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SafeHER: A Safety and Tolerability Study of Assisted and Self-Administered Subcutaneous (SC) Herceptin (Trastuzumab) as Adjuvant Therapy in Early Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01566721
Collaborator
(none)
2,577
Enrollment
437
Locations
2
Arms
93.1
Actual Duration (Months)
5.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This multicenter, two-cohort, non-randomized, open-label study will evaluate the safety and tolerability of assisted and self-administered SC Herceptin as adjuvant therapy in participants with early HER2-positive breast cancer following tumor excision. Participants will receive Herceptin 600 milligrams (mg) SC every 3 weeks for 18 cycles, either by an assisted administration using a conventional syringe and needle/vial formulation (Cohort A) or with assisted and self-administration using a single-use injection device (SID) in selected participants (Cohort B).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
2577 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III Prospective, Two-Cohort Non-Randomized, Multi-Centre, Multinational, Open-Label Study to Assess the Safety of Assisted- and Self-Administered Subcutaneous Trastuzumab as Therapy in Patients With Operable HER2-Positive Early Breast Cancer
Actual Study Start Date :
May 17, 2012
Actual Primary Completion Date :
Mar 10, 2015
Actual Study Completion Date :
Feb 19, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort A: SC Herceptin by Needle/Syringe

Participants will receive SC Herceptin by an assisted administration using a conventional syringe and needle/vial formulation.

Drug: Herceptin
Herceptin will be given as 600 mg SC (into thigh) on Day 1 of each 3-week cycle for up to 18 cycles.
Other Names:
  • Trastuzumab

    		•
    Experimental: Cohort B: SC Herceptin by SID

    Participants will receive SC Herceptin with assisted and/or self-administered use of an SID. The first administration will be performed by a trained healthcare professional. If well tolerated and the participant is willing and judged competent to perform self-administration, subsequent administration of SC Herceptin may be performed by the participant.

    Drug: Herceptin
    Herceptin will be given as 600 mg SC (into thigh) on Day 1 of each 3-week cycle for up to 18 cycles.
    Other Names:
  • Trastuzumab

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With At Least 1 Adverse Event (AE) During the Treatment Period [From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)]

      Participants were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a participant administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. The percentage of participants with at least 1 AE during the treatment period (regardless of severity or seriousness) was reported.

    2. Percentage of Participants With a Grade 3 or Higher AE During the Treatment Period [From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)]

      Participants were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a participant administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. AEs were graded according to National Cancer Institute Common Terminology Criteria Version 4.0. Grade 3 AEs were those considered severe or medically significant but not immediately life-threatening. Grade 4 AEs were those considered life-threatening and/or for which urgent intervention was indicated. Grade 5 AEs were those resulting in death. The percentage of participants with a Grade 3 or higher (i.e., Grade 3 to 5) AE during the treatment period was reported.

    3. Percentage of Participants With Treatment Interruption Due to an AE [From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)]

      Participants were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a participant administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. The percentage of participants with SC Herceptin treatment interrupted to assess or treat AEs was reported.

    4. Number of Herceptin Cycles Received [From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)]

      Participants were planned to receive a total of 18 cycles of SC Herceptin. The median number of cycles actually received was reported.

    5. Percentage of Participants by Total Number of Herceptin Cycles Received [From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)]

      Participants were planned to receive a total of 18 cycles of SC Herceptin. The percentage of participants was reported by the total number of cycles actually received. Because the data are presented non-cumulatively, this table reflects participant distribution by the highest number of cycles received.

    6. Percentage of Participants Who Received Concomitant Cancer Therapy [From Baseline to data cutoff of 10 March 2015 (up to approximately 3 years)]

      Concomitant cancer treatment included chemotherapy, radiotherapy, and hormone therapy administered during the study. The percentage of participants who received any of these concomitant therapies was reported.

    7. Percentage of Participants Who Received Concomitant Non-Cancer Therapy [From Baseline to data cutoff of 10 March 2015 (up to approximately 3 years)]

      Concomitant non-cancer treatment included any pharmacologic interventions administered during the study other than chemotherapy, radiotherapy, or hormone therapy. The percentage of participants who received any concomitant non-cancer therapies was reported.

    Secondary Outcome Measures

    1. Percentage of Participants Who Died by Data Cutoff of 10 March 2015 [From Baseline to time of event (maximum follow-up approximately 3 years as of data cutoff of 10 March 2015)]

      The percentage of participants who died from any cause was reported.

    2. Percentage of Participants Who Died During the Safety Follow-up Period [From Baseline to Time of Event, Safety Follow-Up Period (Up to 6 Years)]

      The percentage of participants who died from any cause was reported during the safety follow-up period.

    3. Disease-Free Survival Rate [From Baseline to time of event (up to approximately 8 years)]

      DFS is defined as the time from first dose of SC Herceptin to the first event of local, regional or distant recurrence, contralateral invasive breast cancer (including ipsilateral ductal carcinoma in situ) or death due to any cause. Time from the date of first dose to any DFS event was expressed in Kaplan-Meier survival probability estimates. Patients without an event will be censored at the last assessment date.

    4. Overall Survival Rate [From Baseline to Time of Event (Up to Approximately 6 Years)]

      Overall survival was defined as the time from randomization to death from any cause. Time from the date of randomization to the date of death was expressed in Kaplan-Meier survival probability estimates. Patients without an event will be censored at the last assessment date.

    5. Percentage of Participants by Item Response to SID Satisfaction Questionnaire [Cycle 4 (cycle length 3 weeks) and last safety follow-up (LSFU) (approximately 1 year)]

      The SID satisfaction questionnaire was administered twice during the study and asked participants to respond to five statements using a Likert scale from "Strongly Disagree" to "Strongly Agree". Questionnaire items were as follows: "I felt comfortable injecting the study drug by myself" (Comfortable), "The SID was convenient and easy to use" (Easy to Use), "I am confident giving myself an injection in the thigh with the SID" (Confident), "Taking all things into account I find self-administration using the SID satisfactory" (Satisfactory), "If given the opportunity I would choose to continue self-injecting the study drug using the SID in the future" (Continue). Participants could only select one response per questionnaire item. There was no calculation of any score, but rather, descriptive summaries were generated by item response. The percentage of participants was reported by the response given for each item on the SID satisfaction questionnaire.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Histologically confirmed early invasive HER2-positive carcinoma of the breast with no evidence of residual, locally recurrent, or metastatic disease and defined as clinical Stage I to IIIC that is eligible for treatment with Herceptin

    • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

    • Screening left ventricular ejection fraction (LVEF) greater than or equal to (≥) 55%

    Exclusion Criteria:

    • Previous neoadjuvant or adjuvant breast cancer treatment with an approved or investigational anti-HER2 agent

    • History of other malignancy except for curatively treated carcinoma in situ of the cervix, basal cell carcinoma, or curatively treated malignancies (other than breast cancer) where the participant has been disease-free for at least 5 years

    • Past history of ductal carcinoma in situ treated with any systemic therapy or with radiation therapy to the ipsilateral breast where invasive cancer subsequently developed

    • Metastatic disease

    • Inadequate bone marrow, hepatic, or renal function

    • Serious cardiac or cardiovascular disease including uncontrolled hypertension or history of hypertensive crisis or hypertensive encephalopathy

    • History of severe allergic or immunological reactions, such as difficult-to-control asthma

    • Pregnant or lactating women

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University "Mother Theresa" Hospital Center; Oncology Department Tirana Albania 1000
    2 CPMC; Service d'Oncologie Médicale Algiers Algeria 16000
    3 Fundación CENIT para la Investigación en Neurociencias Buenos Aires Argentina C1125ABD
    4 Hospital Britanico; Oncologia Buenos Aires Argentina C1280AEB
    5 Instituto De Investigaciones Clinicas Zarate Zarate Argentina 2800
    6 Chris O'Brien Lifehouse Camperdown New South Wales Australia 2050
    7 St George Hospital; Cancer Care Centre Kogarah New South Wales Australia 2217
    8 Prince of Wales Hospital; Oncology Randwick New South Wales Australia 2031
    9 Princess Alexandra Hospital; Division of Cancer Services Woolloongabba Queensland Australia 4102
    10 Queen Elizabeth Hospital; Medical Oncology Woodville South South Australia Australia 5011
    11 Western Hospital Footscray Victoria Australia 3011
    12 Peninsula and South Eastern Haematology and Oncology Group Frankston Victoria Australia 3199
    13 Cabrini Medical Centre; Oncology Malvern Victoria Australia 3144
    14 Royal Perth Hospital; Department of Medical Oncology Perth Western Australia Australia 6000
    15 University Clinical Center of the Republic of Srpska Banja Luka Bosnia and Herzegovina 78000
    16 Clinic of Oncology, University Clinical Center Sarajevo Sarajevo Bosnia and Herzegovina 7100
    17 Hospital Sao Rafael - HSR Salvador BA Brazil 41253-190
    18 Centro de Oncologia da Bahia - CENOB Salvador BA Brazil 41820-021
    19 Hospital Moinhos de Vento Porto Alegre RS Brazil 90035-001
    20 Hospital Amaral Carvalho Jau SP Brazil 17210-120
    21 Instituto do Cancer do Estado de Sao Paulo - ICESP Sao Paulo SP Brazil 01246-000
    22 Hospital Perola Byington Sao Paulo SP Brazil 01317-000
    23 Complex Oncology Center - Plovdiv First Internal Chemotherapy Department Plovdiv Bulgaria 4004
    24 MHAT Serdika; Department of medical oncology Sofia Bulgaria 1303
    25 SHATOD - Sofia Sofia Bulgaria 1784
    26 Cross Cancer Institute ; Dept of Medical Oncology Edmonton Alberta Canada T6G 1Z2
    27 British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre Vancouver British Columbia Canada V5Z 4E6
    28 The Moncton Hospital Moncton New Brunswick Canada E1C 6Z8
    29 Lakeridge Health Oshawa; Oncology Oshawa Ontario Canada L1G 2B9
    30 St. Michael'S Hospital Toronto Ontario Canada M5B 1W8
    31 Windsor Regional Cancer Centre Windsor Ontario Canada N8W 2X3
    32 CSSS champlain - Charles-Le Moyne Greenfield Park Quebec Canada J4V 2H1
    33 Mcgill University - Royal Victoria Hospital; Oncology Montreal Quebec Canada H3A 1A1
    34 Centro Oncológico Antofagasta Antofagasta Chile 1240000
    35 Instituto Nacional del Cancer Santiago Chile 8380000
    36 Sociedad de Investigaciones Medicas Ltda (SIM) Temuco Chile 4800827
    37 Hospital Carlos Van Buren, Servicio de Oncologia Valparaiso Chile 2341391
    38 Clinica del Country Bogota Colombia 11001
    39 Clínica Imbanaco; Oncology Cali Colombia
    40 Clinical Hospital Osijek; Dept For Oncology & Radiotherapy Osijek Croatia 31000
    41 Clinical Hospital Centre Zagreb Zagreb Croatia 10000
    42 Masarykův onkologický ústav; Klinika komplexní onkologické péče Brno Czechia 656 53
    43 Fakultní nemocnice Olomouc Olomouc Czechia 775 20
    44 Fakultní Nemocnice V Motole; Radioterapeuticko-Onkologicke Oddeleni Praha 5 Czechia 150 06
    45 Hospital Metropolitano de Santiago Santiago Dominican Republic 51000
    46 Instituto de Cáncer SOLCA Cuenca; Oncología Cuenca Ecuador EC010107
    47 Solca Guayaquil- Sociedad de Lucha Contra El Cáncer; Oncology Guayaquil Ecuador EC090112
    48 Hospital Solca Quito; Oncologia Quito Ecuador EC170124
    49 Alexandria Uni ; Medical Oncology Alexandria Egypt 11737
    50 Manial Specialized Hospital; Oncology Cairo Egypt 11555
    51 Nci; Oncology Dept Cairo Egypt 11796
    52 Hospital Oncologia; Oncology Salvador El Salvador 01101
    53 HOPITAL JEAN MINJOZ; Oncologie Besancon France 25030
    54 Clinique Tivoli; Sce Radiotherapie Bordeaux France 33000
    55 Polyclinique Bordeaux Nord Aquitaine; Chimiotherapie Radiotherapie Bordeaux France 33077
    56 Ch De Fleyriat; Pneumologie 1 Bourg En Bresse France 01012
    57 Hopital Augustin Morvan; Federation De Cancerologie Brest France 29200
    58 Ch De Brive La Gaillarde; Radiotherapie Oncologie Brive La Gaillarde France 19312
    59 Clinique Sainte Marie; Chimiotherapie Chalon Sur Saone France 71100
    60 Fondation Clement Drevon; Oncology Dijon France 21000
    61 Centre Georges-François Lecler; Ctr de Lutte Contre le Canc Dijon France 21034
    62 Ch De La Dracenie; Hopital De Jour Draguignan France 83007
    63 Hopital Prive Drome Ardeche; Chir 2A 2B Guilherand Granges France 07500
    64 Clinique Sainte Marguerite; Oncologie Medicale Hyeres France 83400
    65 CHD Les Oudairies La Roche Sur Yon France 85925
    66 Hopital Albert Michallon; Oncologie La Tronche France 38700
    67 Ch Du Mans; Medecine Hematologie Oncologie Le Mans France 72037
    68 Clinique Victor Hugo LeMans France 72000
    69 Centre Hartmann Levallois Perret France 92300
    70 Polyclinique Du Bois; Centre Bourgogne Lille France 59000
    71 Hopital Claude Huriez; Medecine Interne Oncologie Lille France 59037
    72 Ch Bretagne Sud Site Scorff; Oncologie Medicale Lorient France 56100
    73 CH Bretagne Sud Site Bodelio; Oncologie Radiotherapie Lorient France 56322
    74 Ctre Consultations La Sauvegarde Lyon France 69338
    75 Hôpital Saint Joseph; Oncologie Medicale Marseille France 13285
    76 CHRA;Hematologie Metz Tessy France 74370
    77 Hopital Clinique Claude Bernard; Oncologie Medicale Metz France 57000
    78 Clinique Clementville; Hopital De Jour Montpellier France 34070
    79 Centre Azureen De Cancerologie; Cons externes Mougins France 06250
    80 Centre Antoine Lacassagne; B3 Medecine Conventionnelle Nice France 06189
    81 Hopital Cochin; Unite Fonctionnelle D Oncologie Paris France 75014
    82 Hopital Hotel Dieu; Oncologie Medicale Paris France 75181
    83 HOPITAL TENON; Cancerologie Medicale Paris France 75970
    84 Ch Francois Mitterrand; Medecine Oncologie Pau France 64046
    85 Ch Lyon Sud; Onco Secteur Jules Courmont Pierre Benite France 69495
    86 Chp Saint Gregoire; Cancerologie Radiotherapie Saint Gregoire France 35768
    87 Ico Rene Gauducheau; Oncologie Saint Herblain France 44805
    88 Clinique de L'Union; Oncologie Saint Jean France 31240
    89 Ch De Saint Quentin; Medecine B10 Saint Quentin France 02321
    90 Institut de Cancerologie de La Loire; Pneumologie Saint-priest-en-jarez France 42270
    91 CMCO De La Cote D Opale; Auberge De Jour St Martin Boulogne France 62280
    92 Centre Paul Strauss; Oncologie Medicale Strasbourg France 67065
    93 Hopitaux Du Leman Site Thonon; Maternite Gynecologie Thonon Les Bains France 74203
    94 Institut Claudius Regaud; Departement Oncologie Medicale Toulouse France 31059
    95 Clinique Pasteur; Pneumologie Toulouse France 31076
    96 Clinique Radio Des Dentellieres; Chimiotherapie Radiotherapie Valenciennes France 59326
    97 Centre-Alexis Vautrin Vandoeuvre-les-Nancy France 54511
    98 Klinikum Augsburg; Frauenklinik Augsburg Germany 86156
    99 Internist; Praxis Für Haemotologie & Onkologie Bad Soden Germany 65812
    100 Praxis Dres. Schilling & Till Berlin Germany 10317
    101 Vivantes Klinikum Am Urban; Zentrum für Brusterkrankungen Berlin Germany 10967
    102 Katholische Hospitalvereinigung Ostwestfalen gGmbH Bielefeld Germany 33615
    103 Gemeinschaftspraxis Dr. Bueckner und Dr. Nueckel Bochum Germany 44787
    104 DONAU ISAR Klinikum Deggendorf; Frauenklinik Deggendorf Germany 94469
    105 Universitätsklinikum Essen; Zentrum Für Frauenheilkunde Essen Germany 45122
    106 Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum Essen Germany 45136
    107 Universitätsklinikum Freiburg; Frauenklinik Freiburg Germany 79106
    108 Klinikum St. Georg GmbH; Franziskus-Hospital Harderberg; Klinik für Gynaekologie und Geburtshilfe Georgsmarienhütte Germany 49124
    109 Krankenhaus St. Elisabeth und St. Barbara, Klinik für Frauenheilkunde und Geburtshilfe Halle Germany 06110
    110 Universitätsklinikum Hamburg-Eppendorf; Zentrum für operative Medizin Klinik für Gynäkologie Hamburg Germany 20246
    111 Kooperatives Mammazentrum Hamburg Krankenhaus Jerusalem Hamburg Germany 20357
    112 Gynaekologisch-Onkologische Schwerpunktpraxis Prof. Dr. med. Lueck, Dr. Schrader und Dr. Noeding Hannover Germany 30177
    113 Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe Hannover Germany 30625
    114 Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg Heidelberg Germany 69120
    115 Universitätsklinikum Jena; Klinik und Poliklinik für Frauenheilkunde und Fortpflanzungsmedizin Jena Germany 07747
    116 Elisabeth-Krankenhaus Brustzentrum Kassel Germany 34117
    117 St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe Koeln Germany 50935
    118 Klinikum Kulmbach; Frauenklinik Kulmbach Germany 95326
    119 Praxis Dr.med. Katja Ziegler-Löhr Köln Germany 50679
    120 Kliniken der Stadt Köln gGmbH Krankenhaus Holweide; Brustzentrum Köln Germany 51067
    121 Dres. Andreas Köhler und Roswitha Fuchs Langen Germany 63225
    122 Klinikum Leverkusen; Med. Klinik III / Onkologie Leverkusen Germany 51375
    123 Klinikum Ludwigsburg; Klinik für Frauenheilkunde und Geburtshilfe Ludwigsburg Germany 71640
    124 Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Klinik für Frauenheilkunde und Geburtshilfe Lübeck Germany 23538
    125 Onkologische Schwerpunktpraxis Lübeck Lübeck Germany 23562
    126 Universitätsmedizin Mainz; Klinik u. Poliklinik f. Geburtshilfe u. Frauenheilkunde Mainz Germany 55131
    127 Gemeinschaftspraxis Fr. Dr. med. Balser & Hr. Dr. med. Weidenbach Marburg Germany 35037
    128 Klinikum Meiningen Klinik f.Gynäkologie und Geburtshilfe Meiningen Germany 98617
    129 Klinikum Memmingen; Abt.Gynäkologie Memmingen Germany 87700
    130 Mühlenkreiskliniken; Johannes Wesling Klinikum Minden; Klinik für Frauenheilkunde und Geburtshilfe Minden Germany 32429
    131 Praxis Dr.med. Steffi Busch Mühlhausen Germany 99974
    132 Gemeinschaftspraxis Prof. Dr.med. Christoph Salat und Dr.med. Oliver J. Stötzer München Germany 80638
    133 Praxis Dr. Prechtl & Dr. Kowolik; Frauenklinik München Germany 81925
    134 Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe Münster Germany 48149
    135 Ruppiner Kliniken, Klinik fuer Gynaekologie und Geburtshilfe Neuruppin Germany 16816
    136 Klinikum Nord Frauenklinik Nürnberg Germany 90419
    137 Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe Offenbach Germany 63069
    138 medius KLINIK OSTFILDERN-RUIT; Brustzentrum Ostfildern Germany 73760
    139 Oncologianova GmbH Recklinghausen Germany 45659
    140 Agaplesion Diakonieklinikum Rotenburg Rotenburg/Wümme Germany 27356
    141 Caritas Klinik St. Theresia -Frauenklinik Brustzentrum Saarbruecken Germany 66113
    142 Leopoldina Krankenhaus der Stadt Schweinfurt GmbH Schweinfurt Germany 97422
    143 HELIOS Klinikum Schwerin; Frauenklinik Schwerin Germany 19049
    144 Johanniter-Krankenhaus Genthin-Stendal; Klinik Für Frauenheilkunde & Geburtshilfe Stendal Germany 39576
    145 Kreiskrankenhaus Torgau; Abt.Gynäkologie und Geburtshilfe Torgau Germany 04860
    146 Universitätsklinik Tübingen; Frauenklinik Tübingen Germany 72076
    147 Katharinen-Hospital gGmbH Unna Germany 59423
    148 GRN-Klinik Weinheim; Abt.Gynäkologie und Geburtshilfe Weinheim Germany 69469
    149 ASKLEPIOS KREISKRANKENHÄUSER WEIßENFELS-HOHENMÖLSEN GMBH Weißenfels Germany 06667
    150 Lahn-Dill Kliniken GmbH Klinikum Wetzlar Gynäkologie/Geburtshilfe Wetzlar Germany 35578
    151 Gesellschaft für Medizinische Studien Würselen Wuerselen Germany 52146
    152 Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine Athens Greece 115 22
    153 Laiko General Hospital; 1St Pathological Clinic Athens Greece 115 27
    154 Alexandras General Hospital of Athens; Oncology Department Athens Greece 115 28
    155 Periph. University General Hospital of Heraklion Crete; Oncology Department Heraklion Greece 711 10
    156 Agioi Anargyroi Cancer Hospital; 2Nd Oncology Dept. Kifisia Greece 145 64
    157 Euromedical General Clinic of Thessaloniki; Oncology Department Thessaloniki Greece 546450
    158 Papageorgiou General Hospital; Medical Oncology Thessaloniki Greece 564 29
    159 Uni Hospital of Alexandroupoli; Dept. of Oncology - Duth Αλεξανδρουπολη Greece 681 00
    160 University Hospital of Larissa; Oncology Λαρισα Greece 413 35
    161 Grupo Angeles Guatemala City Guatemala 01015
    162 Centro Oncológico Sixtino / Centro Oncológico SA Guatemala Guatemala 01010
    163 Queen Elizabeth Hospital; Clinical Oncology Hong Kong Hong Kong
    164 Prince of Wales Hosp; Dept. Of Clinical Onc Shatin Hong Kong
    165 Szent Margit Hospital; Dept. of Oncology Budapest Hungary 1032
    166 Szent Imre Hospital; Dept. of Oncology Budapest Hungary 1115
    167 Orszagos Onkologiai Intezet Budapest Hungary 1122
    168 Semmelweis Egyetem Aok; Iii.Sz. Belgyogyaszati Klinika Budapest Hungary 1125
    169 Debreceni Egyetem Klinikai Kozpont ; Department of Oncology Debrecen Hungary 4032
    170 Josa Andras Korhaz; Dept of Oncoradiology Nyíregyháza Hungary 4400
    171 Pécsi Tudományegyetem; Klinikai Központ Onkoterápiás Intézet Pécs Hungary 7623
    172 Markusovszky Hospital Szombathely Hungary 9700
    173 Hasan Sadikin Hospital; Internal Medicine Bandung Indonesia 40161
    174 CiptoMangunkusumo Hospital; Internal Medicine Central Jakarta Indonesia 10430
    175 Soetomo Hospital; Surgery East Java Indonesia 60286
    176 Dharmais National Cancer Center Jakarta Indonesia 11420
    177 Sardjito Hospital; Instalasi Kanker Tulip Jogjakarta Indonesia 55284
    178 Mater Misericordiae Uni Hospital; Oncology Dublin Ireland 7
    179 Mater Private Hospital Dublin Ireland 7
    180 Beaumont Hospital; Cancer Clinical Trials Unit Dublin Ireland 9
    181 University Hospital Limerick Limerick City Ireland
    182 Sligo General Hospital; Oncology Sligo Ireland
    183 Waterford Regional Hospital; Department Of Medical Oncology Waterford Ireland
    184 Ospedale Oncologico Regionale; U.O. Oncologia Medica Ed Ematologia Rionero in Vulture Basilicata Italy 85028
    185 Azienda Ospedaliera A. Cardarelli Napoli Campania Italy 80131
    186 Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica Napoli Campania Italy 80131
    187 Università degli Studi Federico II; Clinica di Oncologia Medica Napoli Campania Italy 80131
    188 IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica Meldola Emilia-Romagna Italy 47014
    189 Ospedale Regionale Di Parma; Divisione Di Oncologia Medica Parma Emilia-Romagna Italy 43100
    190 Az. Osp. Ospedale Civile; U.O. Di Oncologia Medica Ed Ematologia Piacenza Emilia-Romagna Italy 29100
    191 Azienda USL di Ravenna; Unità Operativa di Oncologia Medica Ravenna Emilia-Romagna Italy 48100
    192 Ausl Frosinone - Ospedale Umberto I; Divisione Di Oncologia Frosinone Lazio Italy 03100
    193 IFO - Istituto Regina Elena; Oncologia Medica Roma Lazio Italy 00144
    194 Policlinico Umberto i di Roma; dip. Scienze Radiologiche, Oncologiche, Anatomopatologiche Roma Lazio Italy 00161
    195 Azienda Ospedaliera Sant'Andrea Roma Lazio Italy 00189
    196 Ospedale Belcolle Di Viterbo; Oncologia Viterbo Lazio Italy 01100
    197 Asst Papa Giovanni XXIII; Oncologia Medica Bergamo Lombardia Italy 24127
    198 ASST DI CREMONA; Unità di Patologia Mammaria Senologia e Breast Unit Cremona Lombardia Italy 26100
    199 Fondazione IRCCS Istituto Nazionale dei Tumori; S. C. Oncologia Medica 2 Milano Lombardia Italy 20133
    200 ASST DI MONZA; Oncologia Medica Monza Lombardia Italy 20900
    201 IRRCCS San Matteo; Dip Oncoematologico ; Divisione Oncologia Pavia Lombardia Italy 27100
    202 IRCCS Istituto Clinico Humanitas; Oncologia Rozzano Lombardia Italy 20089
    203 A.O. Città della Salute e della Scienza - Presidio Molinette; divisione oncologia medica Torino Piemonte Italy 10126
    204 Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica Bari Puglia Italy 70124
    205 Ospedale Vito Fazzi; Div. Oncoematologia Lecce Puglia Italy 73100
    206 IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia San Giovanni Rotondo Puglia Italy 71013
    207 Ospedale Oncologico A.Businco; Div. Oncologia Medica II Cagliari Sardegna Italy 09121
    208 Ospedale Civile SS Annunziata; oncologia medica Sassari Sardegna Italy 07100
    209 Ospedale Garibaldi Nesima; Biomedicina Clinica e Molecolare Catania Sicilia Italy 95100
    210 Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1 Firenze Toscana Italy 50139
    211 Azlenda Ospendaliero-Universitaria Pisana; C.O. Oncologia 2 Pisa Toscana Italy 56100
    212 Azienda usl 5 Di Pisa-Ospedale Di Pontedera;U.O. Oncologia Pontedera Toscana Italy 56025
    213 Ospedale Civile; Oncologia Medica Camposampiero Veneto Italy 35012
    214 Arcispedale S.Anna; Oncologia Medica Cona (Ferrara) Veneto Italy 44124
    215 National Cancer Center Goyang-si Korea, Republic of 10408
    216 Samsung Medical Center Seoul Korea, Republic of (0)6351
    217 Korea University Guro Hospital Seoul Korea, Republic of 08308
    218 Yonsei University Severance Hospital; Medical Oncology Seoul Korea, Republic of 120-752
    219 Asan Medical Center. Seoul Korea, Republic of 138-736
    220 Hospital of Lithuanian University of Health. Sciences Kaunas Clinics Kaunas Lithuania 50009
    221 Klaipeda University Hospital Klaipeda Lithuania 92288
    222 Hospital Pulau Pinang; Jabatan Radioterapi & Onkologi Georgetown Malaysia 10990
    223 University Malaya Medical Centre; Clinical Oncology Unit, Kuala Lumpur Malaysia 59100
    224 Hospital Wanita dan Kanak-Kanak Sabah Sabah Malaysia 88996
    225 Sarawak General Hospital; Department of Radiotherapy, Oncology and Palliative care Sarawak Malaysia 93586
    226 Centro Estatal de Oncología de Campeche Campeche Mexico 24096
    227 Centro Estatal de Cancerología Chihuahua Mexico 31000
    228 Instituto Nacional de Cancerologia; Oncology Distrito Federal Mexico 14080
    229 Consultorio de Medicina Especializada; Dentro de Condominio San Francisco Mexico City Mexico 03100
    230 Oaxaca Site Management Organization Oaxaca Mexico 68000
    231 Cancerologia de Queretaro; Oncologia Queretaro, Queretaro Mexico 76090
    232 Centro Estatal de Cancerologia de Nayarit Tepic Mexico 63170
    233 Institut National D'oncologie Sidi Med Benabdellah Rabat Morocco 6213
    234 Jeroen Bosch Ziekenhuis 'S Hertogenbosch Netherlands 5223 GZ
    235 Onze Lieve Vrouwe Gasthuis AC Amsterdam Netherlands 1091
    236 Gelre Ziekenhuis Apeldoorn, Lokatie Lukas; Afdeling Interne Geneeskunde Apeldoorn Netherlands 7334 DZ
    237 Rijnstate Ziekenhuis; Inwendige Geneeskunde Arnhem Netherlands 6815 AD
    238 Albert Schweitzer Ziekenhuis - loc Dordrecht Dordrecht Netherlands 3318 AT
    239 Ziekenhuis Gelderse Vallei; Inwendige Geneeskunde EDE Netherlands 6716 RP
    240 Catharina Ziekenhuis; Dept of Internal Medicin Eindhoven Netherlands 5623 EJ
    241 Maxima Medisch Centrum; Inwendige Geneeskunde Eindhoven Netherlands 5631 BM
    242 Martini Ziekenhuis; Dept of Internal Medicine Groningen Netherlands 9728 NT
    243 Atrium Medisch Centrum Parkstad, Heerlen Heerlen Netherlands 6419 PC
    244 Spaarne Ziekenhuis; Inwendige Geneeskunde Hoofddorp Netherlands 2134 TM
    245 St. Antonius Ziekenhuis Nieuwegein Nieuwegein Netherlands 3435 CM
    246 Franciscus Ziekenhuis Roosendaal Netherlands 4708 AE
    247 Maasstad ziekenhuis; Afdeling oncologie hematologie Rotterdam Netherlands 3079 DZ
    248 Ikazia Ziekenhuis Rotterdam Netherlands 3083 AN
    249 Vlietland Ziekenhuis, Locatie Schiedam; Interne Geneeskunde Schiedam Netherlands 3100 AE
    250 Zuyderland ziekenhuis locatie Geleen Sittard-Geleen Netherlands 6162 BG
    251 Diakonessenhuis Utrecht: ziekenhuisapotheek Utrecht Netherlands 3582 KE
    252 Ziekenhuis VieCurie Vitaal Venlo Netherlands 5912 BL
    253 Zaans Medisch Centrum Zaandam Netherlands 1502 DV
    254 Tauranga Hospital, Clinical Trials Unit; BOP Clinical School Tauranga New Zealand 3112
    255 Sørlandet Sykehus Kristiansand Kristiansand Norway 4604
    256 Oslo universitetssykehus HF, Ullevål, Kreftsenteret Oslo Norway 0450
    257 Helse Stavanger HF, Stavanger Universitetssjukehus; Klinikk for Blod og kreftsykdommer Stavanger Norway 4011
    258 Shifa International Hospital; Department of Oncology Islamabad Pakistan 44000
    259 Aga Khan University; Department of Oncology Karachi Pakistan 74800
    260 Shaukat Khanum Memorial Cancer Hospital; Department of Oncology Lahore Pakistan 54000
    261 Hameed Latif Hospital; Department of Oncology Lahore Pakistan 54600
    262 Centro Hemato Oncologico Panama Panama Panama 0832
    263 Centro Medico Monte Carmelo Arequipa Peru 04001
    264 Instituto Nacional de Enfermedades Neoplasicas Lima Peru Lima 34
    265 Clinica de Especialidades Medicas Lima Peru Lima 41
    266 Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional Lima Peru Lima 41
    267 Instituto Oncologico de Lima LIma Peru Lima27
    268 Philippine General Hospital; Section Of Medical Oncology Manila Philippines 1000
    269 East Avenue Medical Center Quezon City Philippines 1100
    270 Poradnia Onkologiczna oraz Oddzial Kliniczny Onkologii SPZOZ Szpital Uniwersytecki Kraków Poland 30-688
    271 Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii Otwock Poland 05-400
    272 Oddzial Chemioterapii Szpitala Klinicznego Nr 1 w Poznaniu Poznan Poland 60-569
    273 Wielkopolskie Centrum Onkologi Poznan Poland 61-866
    274 MRUKMED Lekarz Beata Madej-Mruk i Partner Spolka Partnerska Oddzial nr 1 w Rzeszowie Rzeszow Poland 35-021
    275 Wojewodzki Szpital Zespolony Torun Poland 87-100
    276 NZOZ Onko-Dent SP. P. G. L. Slomian, Poradnia Onkologiczna Zory Poland 44-240
    277 Centro Clinico Champalimaud; Oncologia Medica Lisboa Portugal 1400-038
    278 Hospital da Luz; Departamento de Oncologia Medica Lisboa Portugal 1500-650
    279 IPO do Porto; Servico de Oncologia Medica Porto Portugal 4200-072
    280 Hospital de Sao Joao; Servico de Oncologia Porto Portugal 4200-319
    281 Policlinica Sfanta Maria - Oncology; Medical Oncology Baia Mare Romania 430241
    282 Emergency University Bucharest Hospital; Oncology Department Bucharest Romania 050098
    283 Institut of Oncology Al. Trestioreanu Bucharest; Oncology Department Bucuresti Romania 022328
    284 Prof. Dr. I. Chiricuta Institute of Oncology Cluj Napoca Romania 400015
    285 Cluj Clinical County Hospital; Oncology Dept Cluj-Napoca Romania 400006
    286 SC Oncolab SRL Craiova Romania 200385
    287 Clinical Hospital 1 Craiova; Medical Oncology Craiova Romania 200642
    288 S.C. Life Search S.R.L; Medical Oncology Clinic Timisoara Romania 300167
    289 ONCOMED - Medical Centre Timisoara Romania 300239
    290 Regional Oncology Hospital Irkutsk Russian Federation 664035
    291 City Oncological Hospital Izhevsk Russian Federation 426009
    292 Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy Moscow Russian Federation 115478
    293 City Clinical Oncology Hospital Moscow Russian Federation 143423
    294 State Inst. Of Healthcare Orenburg Regional Clinical Oncology Dis Orenburg Russian Federation 460021
    295 City Clinical Oncology Dispensary, SPb SBIH CCOD Saint-Petersburg Russian Federation 198255
    296 Bashkirian Republican Clinical Oncology Dispensary UFA Russian Federation 450054
    297 King Faisal Specialist Hospital & Research Centre Jeddah Saudi Arabia 21499
    298 King Abdul Aziz Medical City, King Fahd National Guard; Oncology Riyadh Saudi Arabia 22490
    299 Clinical Hospital Center Bezanijska kosa; Clinic for Oncology Belgrade Serbia 11000
    300 Institute for Onc/Rad Serbia Belgrade Serbia 11000
    301 Clinical Center Kragujevac Kragujevac Serbia 34000
    302 Clinical Centre Nis, Clinic for Oncology Nis Serbia 18000
    303 Oncology Institute of Vojvodina Sremska Kamenica Serbia 21204
    304 National Cancer Centre; Medical Oncology Singapore Singapore 169610
    305 Mammacentrum sv. Agáty Banská Bystrica Slovakia 974 01
    306 National Cancer Institute - Comenius University; Dept. Clinical Oncology Bratislava Slovakia 811 05
    307 Vychodoslovensky onkologicky ustav Košice Slovakia 040 01
    308 Fakultna nemocnica s poliklinikou J.A. Reimana Presov Presov Slovakia 081 81
    309 Fakultna nemocnica Trencín; Onkologicke odd. Trencin Slovakia 911 71
    310 University Medical Centre Maribor; Depart. of Gynecology & Breast Oncology Maribor Slovenia 2000
    311 Westridge Medical Center Durban South Africa 4058
    312 Donald Gordon Medical Centre Johannesburg South Africa 2193
    313 Steve Biko Academic Hospital; Oncology Pretoria South Africa 0002
    314 Hospital General de Elda; Servicio de Oncologia Elda Alicante Spain 03600
    315 Hospital de Cabueñes; Servicio de Oncologia Gijon Asturias Spain 33394
    316 Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia Badalona Barcelona Spain 08916
    317 Corporacio Sanitaria Parc Tauli; Servicio de Oncologia Sabadell Barcelona Spain 8208
    318 Hospital Universitario Marques de Valdecilla; Servicio de Oncologia Santander Cantabria Spain 39008
    319 IInstituto Oncologico de San Sebastian, Oncologikoa; Servicio de Oncologia San Sebastian Guipuzcoa Spain 20014
    320 Hospital Universitario Son Espases Palma De Mallorca Islas Baleares Spain 07014
    321 Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Oncologia Las Palmas de Gran Canaria LAS Palmas Spain 35016
    322 Hospital de Gran Canaria Dr. Negrin; Servicio de Oncologia Las Palmas de Gran Canaria LAS Palmas Spain 35020
    323 Hospital Quiron de Madrid; Servicio de Oncologia Pozuelo de Alarcon Madrid Spain 28223
    324 Hospital Do Meixoeiro; Servicio de Oncologia Vigo Pontevedra Spain 36214
    325 Hospital Universitario de Canarias;servicio de Oncologia La Laguna Tenerife Spain 38320
    326 Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Oncologia Santa Cruz de Tenerife Tenerife Spain 38010
    327 Hospital Lluis Alcanys; Servicio de Oncologia Xativa Valencia Spain 46800
    328 Hospital de Basurto; Servicio de Oncologia Bilbao Vizcaya Spain 48013
    329 Complejo Hospitalario Universitario de Albacete; Servicio de Oncologia Albacete Spain 02006
    330 Hospital General Univ. de Alicante; Servicio de Oncologia Alicante Spain 3010
    331 Hospital del Mar; Servicio de Oncologia Barcelona Spain 08003
    332 Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia Barcelona Spain 08041
    333 Hospital Duran i Reynals; Oncologia Barcelona Spain 08907
    334 Complejo Asistencial Universitario De Burgos; Servicio de Oncologia Burgos Spain 09006
    335 Hospital San Pedro De Alcantara; Servicio de Oncologia Caceres Spain 10003
    336 Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia Jaen Spain 23007
    337 Complejo Asistencial Universitario de Leon; Servicio de Oncologia Leon Spain 24071
    338 Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia Lerida Spain 25198
    339 Hospital Ramon y Cajal; Servicio de Oncologia Madrid Spain 28034
    340 Hospital Universitario Clínico San Carlos; Servicio de Oncologia Madrid Spain 28040
    341 HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia Madrid Spain 28050
    342 Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia Murcia Spain 30120
    343 Hospital de Navarra; Servicio de Oncologia Navarra Spain 31008
    344 Complejo Hospitalario de Toledo- H. Virgen de la Salud; Servicio de Oncologia Toledo Spain 45004
    345 Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia Valencia Spain 46015
    346 Hospital Clinico Universitario Lozano Blesa; Servicio de Oncologia Zaragoza Spain 50009
    347 Skånes University Hospital, Skånes Department of Onclology Lund Sweden 221 85
    348 Skaraborgs sjukhus Skoevde, Dept of surgery Skoevde Sweden 54185
    349 Hirslanden Medical Center, Tumorzentrum Aarau Switzerland 5000
    350 Kantonsspital Baden; Frauenklinik Baden Switzerland 5405
    351 Ospedale San Giovanni; Oncologia Bellinzona Switzerland 6500
    352 Inselspital Bern; Universitätsklinik für medizinische Onkologie Bern Switzerland 3010
    353 Kantonsspital Frauenfeld, Frauenklinik Thurgau Frauenfeld Switzerland 8501
    354 CHUV; Departement d'Oncologie Lausanne Switzerland 1011
    355 Spital Thun; Medizinische Klinik Thun Switzerland 3600
    356 Kantonsspital Winterthur; Medizinische Onkologie Winterthur Switzerland 8401
    357 Stadtspital Triemli; Frauenklinik Zürich Switzerland 8063
    358 China Medical University Hospital; Surgery Taichung Taiwan 404
    359 National Cheng Kung Uni Hospital; Surgery Tainan Taiwan 704
    360 National Taiwan Uni Hospital; General Surgery Taipei Taiwan 100
    361 Tri-Service General Hospital, Division of General Surgery Taipei Taiwan 114
    362 Department of Surgery, King Chulalongkorn Memorial Hospital Bangkok Thailand 10330
    363 Pramongkutklao Hospital; Medicine - Medical Oncology Unit Bangkok Thailand 10400
    364 Rajvithi Hospital Bangkok Thailand 10400
    365 Ramathibodi Hospital; Medicine/Oncology Bangkok Thailand 10400
    366 Maharaj Nakorn Chiang Mai Hospital; Department of Surgery/Head Neck and Breast Unit; Clinical Trial Chiang Mai Thailand 50200
    367 Oncology Unit, Faculty of Medicine, Vajira Hospital; Department of Medicine Dusit Thailand 10300
    368 Ankara Uni School of Medicine; Medical Oncology Ankara Turkey 06590
    369 Akdeniz University Medical Faculty; Medical Oncology Department Antalya Turkey 07070
    370 Dicle University Faculty of Medicine Diyarbakir Turkey 21280
    371 Gaziantep Univ. Med. Fac. Gaziantep Turkey 27310
    372 Istanbul Uni of Medicine Faculty; Oncology Dept Istanbul Turkey 34390
    373 Marmara Uni Faculty of Medicine; Medical Oncology Istanbul Turkey 34890
    374 Kocaeli University Faculty of Medicine; Medical oncology Izmit Turkey 31380
    375 Mersin University Medical Faculty Mersin Turkey 33169
    376 19 Mayis University Medical Faculty; Medical Oncology Department Samsun Turkey 55139
    377 Hacettepe Uni Medical Faculty Hospital; Oncology Dept Sihhiye/Ankara Turkey 06230
    378 Kyiv City Clinical Oncological Center; Chemotherapy Department Kiev Ukraine 03115
    379 State Oncology Regional Treatment-Diagnostic Center; Chemotherapy Department Lviv Ukraine 79031
    380 Tawam Hospital Al Ain United Arab Emirates 15258
    381 Nevill Hall Hospital Abergavenny United Kingdom NP7 7EG
    382 Bedford Hospital; Oncology Bedford United Kingdom MK42 9DJ
    383 Wexham Park Hospital; Oncology Berkshire United Kingdom SL2 4HL
    384 University Hospital Birmingham Queen Elizabeth Hospital Birmingham United Kingdom B17 0NH
    385 Heartlands Hospital; Department Of Medicine Birmingham United Kingdom B9 5SS
    386 Royal Bournemouth Hospital; Oncology Bournemouth United Kingdom BH7 7DW
    387 Kent & Canterbury Hospital Canterbury United Kingdom CT1 3NG
    388 Broomfield Hospital; Oncology Chelmsford United Kingdom CM1 7ET
    389 Glan Clwyd Distr Gen Hospital;Nth Wales Cancer Treatment Ctr Denbighshire United Kingdom LL18 5UJ
    390 Royal Derby Hospital Derby United Kingdom DE22 3NE
    391 North Devon District Hospital Devon United Kingdom EX31 4JB
    392 Russells Hall Hospital; Oncology Dudley United Kingdom DY1 2HQ
    393 University Hospital of North Durham Durham United Kingdom DH15TW
    394 Beatson West of Scotland Cancer Centre Glasgow United Kingdom G12 0YN
    395 Inverclyde Hospital Greenock United Kingdom PA16 0XN
    396 Diana Princess of Wales Hosp. Grimsby United Kingdom DN33 2BA
    397 Royal Surrey County Hospital Guildford United Kingdom GU2 7XX
    398 Princess Alexandra Hospital; Oncology Department Harlow United Kingdom CM20 1QX
    399 Huddersfield Royal Infirmary Huddersfield United Kingdom HD3 3EA
    400 Ipswich Hospital Ipswich United Kingdom IP4 5PD
    401 Crosshouse Hospital; Dept of Oncology Kilmarnock United Kingdom KA2 0BE
    402 Forth Valley Royal Hospital ; Oncology Department Larbert United Kingdom FK5 4QE
    403 Leicester Royal Infirmary Leicester United Kingdom LE1 5WW
    404 St John's Hospital Livingston United Kingdom EH54 6PP
    405 Guys and St Thomas NHS Foundation Trust, Guys Hospital London United Kingdom SE1 9RT
    406 Queen Elizabeth Hospital London United Kingdom SE18 4QH
    407 St George's Hospital London United Kingdom SW17 0QT
    408 Macclesfield District General Hospital Macclesfield United Kingdom SK10 3BL
    409 Christie Hospital; Breast Cancer Research Office Manchester United Kingdom M20 4QL
    410 Freeman Hospital; Northern Centre For Cancer Care New Castle Upon Tyne United Kingdom NE7 7DN
    411 Royal Gwent Hospital Newport United Kingdom NP20 2UB
    412 North Tyneside General Hospital North Shields United Kingdom NE29 8NH
    413 Northampton General Hospital NHS Trust Northampton United Kingdom NN1 5BD
    414 Derriford Hospital; Plymouth Oncology Centre Plymouth United Kingdom PL6 8DH
    415 Poole General Hospital Poole United Kingdom BH15 2JB
    416 Queen Alexandra Hospital, Portsmouth Portsmouth United Kingdom PO6 3LY
    417 Royal Preston Hospital Preston United Kingdom PR2 9HT
    418 Queens Hospital; R&D Romford United Kingdom RM7 0AE
    419 Scarborough General Hospital Scarborough United Kingdom YO12 6QL
    420 Royal Shrewsbury Hospital; Pharmacy Department Shrewsbury United Kingdom SY3 8XQ
    421 Southampton General Hospital Southampton United Kingdom SO16 6YD
    422 Sunderland Royal Hospital Sunderland United Kingdom SR4 7TP
    423 Singleton Hospital; Pharmacy Department Swansea United Kingdom SA2 8QA
    424 Great Western Hospital, Swindon Cancer Research Unit; Osprey Unit Level 3 Swindon United Kingdom SN3 6BB
    425 Royal Cornwall Hospital Truro United Kingdom TR1 3LQ
    426 Royal Hampshire County Hospital; Winchester & Andover Breast Unit Winchester United Kingdom SO22 5DG
    427 The Clatterbridge Cancer Ctr For Oncolgy Wirral United Kingdom CH63 4JY
    428 The Royal Wolverhampton Hospitals NHS Trust Wolverhampton United Kingdom WV10 0QP
    429 Airedale General Hospital; Oncology York United Kingdom BD20 6TD
    430 York District Hospital York United Kingdom YO31 8HE
    431 Grupo Oncológico Cooperativo Uruguayo; Hospital de Clínicas - Dpto. de Oncología Montevideo Uruguay 11400
    432 Hospital Militar; Oncologia Montevideo Uruguay 11600
    433 Hospital Pereira Rossell; Oncology Department Montevideo Uruguay 11600
    434 Instituto Oncológico Luis Razetti Caracas Venezuela 1010
    435 Centro Integral de Oncología Caracas Venezuela 1060
    436 Centro Médico Docente La Trinidad; Unidad de Protocolos Clínicos Caracas Venezuela 1080
    437 K hospital Hanoi Vietnam 100000

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT01566721
    Other Study ID Numbers:
    • MO28048
    • 2011-005328-17
    First Posted:
    Mar 29, 2012
    Last Update Posted:
    Apr 27, 2021
    Last Verified:
    Apr 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:
    Breast Neoplasms
    Trastuzumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Of the 2984 participants screened, a total of 2577 participants were enrolled into the trial, and 2573 participants received at least one dose of study treatment. 4 Participants were not included in the Safety Follow-Up (SFU) ITT due to the lack of Principal Investigator signatures.
    Arm/Group Title Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Arm/Group Description Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe. Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by a healthcare professional (HCP). Subsequent doses were self-administered by participants who were willing and judged competent by the HCP.
    Period Title: Treatment Period
    STARTED 1867 710
    COMPLETED 1670 652
    NOT COMPLETED 197 58
    Period Title: Treatment Period
    STARTED 1865 708
    COMPLETED 1318 501
    NOT COMPLETED 547 207

    Baseline Characteristics

    Arm/Group Title Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SID Total
    Arm/Group Description Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe. Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by participants who were willing and judged competent by the HCP. Total of all reporting groups
    Overall Participants 1867 710 2577
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    54.0
    (12.01)
    53.0
    (11.32)
    53.7
    (11.83)
    Sex: Female, Male (Count of Participants)
    Female
    1863
    99.8%
    710
    100%
    2573
    99.8%
    Male
    4
    0.2%
    0
    0%
    4
    0.2%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With At Least 1 Adverse Event (AE) During the Treatment Period
    Description Participants were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a participant administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. The percentage of participants with at least 1 AE during the treatment period (regardless of severity or seriousness) was reported.
    Time Frame From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)

    Outcome Measure Data

    Analysis Population Description
    Safety Population: All enrolled participants who received at least one dose of study medication according to assigned treatment.
    Arm/Group Title Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SID
    Arm/Group Description Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe. Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by participants who were willing and judged competent by the HCP.
    Measure Participants 1864 709
    Number [percentage of participants]
    88.6
    4.7%
    89.0
    12.5%
    2. Primary Outcome
    Title Percentage of Participants With a Grade 3 or Higher AE During the Treatment Period
    Description Participants were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a participant administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. AEs were graded according to National Cancer Institute Common Terminology Criteria Version 4.0. Grade 3 AEs were those considered severe or medically significant but not immediately life-threatening. Grade 4 AEs were those considered life-threatening and/or for which urgent intervention was indicated. Grade 5 AEs were those resulting in death. The percentage of participants with a Grade 3 or higher (i.e., Grade 3 to 5) AE during the treatment period was reported.
    Time Frame From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)

    Outcome Measure Data

    Analysis Population Description
    Safety Population
    Arm/Group Title Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SID
    Arm/Group Description Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe. Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by participants who were willing and judged competent by the HCP.
    Measure Participants 1864 709
    Number (95% Confidence Interval) [percentage of participants]
    24.0
    1.3%
    21.0
    3%
    3. Primary Outcome
    Title Percentage of Participants With Treatment Interruption Due to an AE
    Description Participants were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a participant administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. The percentage of participants with SC Herceptin treatment interrupted to assess or treat AEs was reported.
    Time Frame From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)

    Outcome Measure Data

    Analysis Population Description
    Safety Population
    Arm/Group Title Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SID
    Arm/Group Description Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe. Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by participants who were willing and judged competent by the HCP.
    Measure Participants 1864 709
    Number [percentage of participants]
    9.8
    0.5%
    10.4
    1.5%
    4. Primary Outcome
    Title Number of Herceptin Cycles Received
    Description Participants were planned to receive a total of 18 cycles of SC Herceptin. The median number of cycles actually received was reported.
    Time Frame From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)

    Outcome Measure Data

    Analysis Population Description
    Safety Population. The endpoint also included an analysis of a subgroup of participants from Cohort B who received doses of self-administered SC Herceptin via SID.
    Arm/Group Title Cohort B: SC Herceptin by SID (Self-Administered) Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SID
    Arm/Group Description Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. Dosing was either performed by self-administration or a qualified HCP. The present subgroup included only participants for whom SC Herceptin was given by self-administration. Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe. Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by participants who were willing and judged competent by the HCP.
    Measure Participants 550 1864 709
    Median (Full Range) [cycles]
    16.0
    18.0
    18.0
    5. Primary Outcome
    Title Percentage of Participants by Total Number of Herceptin Cycles Received
    Description Participants were planned to receive a total of 18 cycles of SC Herceptin. The percentage of participants was reported by the total number of cycles actually received. Because the data are presented non-cumulatively, this table reflects participant distribution by the highest number of cycles received.
    Time Frame From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)

    Outcome Measure Data

    Analysis Population Description
    Safety Population. The endpoint also included an analysis of a subgroup of participants from Cohort B who received doses of self-administered SC Herceptin via SID.
    Arm/Group Title Cohort B: SC Herceptin by SID (Self- Administered) Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SID
    Arm/Group Description Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. Dosing was either performed by self-administration or a qualified HCP. The present subgroup included only participants for whom SC Herceptin was given by self- administration. Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe. Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by participants who were willing and judged competent by the HCP.
    Measure Participants 550 1864 709
    1 Cycle Received
    2.7
    0.1%
    1.0
    0.1%
    0.8
    0%
    2 Cycles Received
    1.3
    0.1%
    0.5
    0.1%
    0.4
    0%
    3 Cycles Received
    1.1
    0.1%
    0.5
    0.1%
    0.1
    0%
    4 Cycles Received
    1.6
    0.1%
    1.2
    0.2%
    0.7
    0%
    5 Cycles Received
    1.3
    0.1%
    0.8
    0.1%
    0.6
    0%
    6 Cycles Received
    1.6
    0.1%
    0.5
    0.1%
    0.1
    0%
    7 Cycles Received
    2.2
    0.1%
    0.7
    0.1%
    0.8
    0%
    8 Cycles Received
    2.2
    0.1%
    0.9
    0.1%
    0.3
    0%
    9 Cycles Received
    1.8
    0.1%
    0.2
    0%
    0.6
    0%
    10 Cycles Received
    1.5
    0.1%
    0.3
    0%
    0.1
    0%
    11 Cycles Received
    3.5
    0.2%
    0.4
    0.1%
    0.3
    0%
    12 Cycles Received
    2.5
    0.1%
    0.9
    0.1%
    0.8
    0%
    13 Cycles Received
    4.9
    0.3%
    0.2
    0%
    0
    0%
    14 Cycles Received
    6.9
    0.4%
    0.5
    0.1%
    0.6
    0%
    15 Cycles Received
    10.7
    0.6%
    0.5
    0.1%
    0.4
    0%
    16 Cycles Received
    21.6
    1.2%
    0.6
    0.1%
    0.3
    0%
    17 Cycles Received
    32.5
    1.7%
    1.0
    0.1%
    1.1
    0%
    18 Cycles Received
    0
    0%
    89.2
    12.6%
    91.8
    3.6%
    19 Cycles Received
    0
    0%
    0.2
    0%
    0
    0%
    6. Primary Outcome
    Title Percentage of Participants Who Received Concomitant Cancer Therapy
    Description Concomitant cancer treatment included chemotherapy, radiotherapy, and hormone therapy administered during the study. The percentage of participants who received any of these concomitant therapies was reported.
    Time Frame From Baseline to data cutoff of 10 March 2015 (up to approximately 3 years)

    Outcome Measure Data

    Analysis Population Description
    Safety Population
    Arm/Group Title Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SID
    Arm/Group Description Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe. Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by participants who were willing and judged competent by the HCP.
    Measure Participants 1864 709
    Chemotherapy
    58.2
    3.1%
    63.9
    9%
    Radiotherapy
    51.3
    2.7%
    48.5
    6.8%
    Hormone Therapy
    53.5
    2.9%
    50.4
    7.1%
    7. Primary Outcome
    Title Percentage of Participants Who Received Concomitant Non-Cancer Therapy
    Description Concomitant non-cancer treatment included any pharmacologic interventions administered during the study other than chemotherapy, radiotherapy, or hormone therapy. The percentage of participants who received any concomitant non-cancer therapies was reported.
    Time Frame From Baseline to data cutoff of 10 March 2015 (up to approximately 3 years)

    Outcome Measure Data

    Analysis Population Description
    Safety Population
    Arm/Group Title Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SID
    Arm/Group Description Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe. Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by participants who were willing and judged competent by the HCP.
    Measure Participants 1864 709
    Number [percentage of participants]
    89.1
    4.8%
    89.7
    12.6%
    8. Secondary Outcome
    Title Percentage of Participants Who Died by Data Cutoff of 10 March 2015
    Description The percentage of participants who died from any cause was reported.
    Time Frame From Baseline to time of event (maximum follow-up approximately 3 years as of data cutoff of 10 March 2015)

    Outcome Measure Data

    Analysis Population Description
    ITT Population
    Arm/Group Title Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SID
    Arm/Group Description Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe. Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by participants who were willing and judged competent by the HCP.
    Measure Participants 1867 710
    Number [percentage of participants]
    1.5
    0.1%
    0.8
    0.1%
    9. Secondary Outcome
    Title Percentage of Participants Who Died During the Safety Follow-up Period
    Description The percentage of participants who died from any cause was reported during the safety follow-up period.
    Time Frame From Baseline to Time of Event, Safety Follow-Up Period (Up to 6 Years)

    Outcome Measure Data

    Analysis Population Description
    ITT Population
    Arm/Group Title Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SID
    Arm/Group Description Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe. Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by participants who were willing and judged competent by the HCP.
    Measure Participants 1865 708
    Number [Percentage of Participants]
    6.8
    0.4%
    7.3
    1%
    10. Secondary Outcome
    Title Disease-Free Survival Rate
    Description DFS is defined as the time from first dose of SC Herceptin to the first event of local, regional or distant recurrence, contralateral invasive breast cancer (including ipsilateral ductal carcinoma in situ) or death due to any cause. Time from the date of first dose to any DFS event was expressed in Kaplan-Meier survival probability estimates. Patients without an event will be censored at the last assessment date.
    Time Frame From Baseline to time of event (up to approximately 8 years)

    Outcome Measure Data

    Analysis Population Description
    ITT Population who completed Safety Follow-up
    Arm/Group Title Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SID
    Arm/Group Description Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe. Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by participants who were willing and judged competent by the HCP.
    Measure Participants 1865 708
    0.5 Year
    0.990
    0.987
    1 Year
    0.975
    0.976
    1.5 Year
    0.960
    0.957
    2 Years
    0.934
    0.939
    3 Years
    0.904
    0.896
    4 Years
    0.881
    0.874
    5 Years
    0.868
    0.863
    6 Years
    0.851
    0.853
    11. Secondary Outcome
    Title Overall Survival Rate
    Description Overall survival was defined as the time from randomization to death from any cause. Time from the date of randomization to the date of death was expressed in Kaplan-Meier survival probability estimates. Patients without an event will be censored at the last assessment date.
    Time Frame From Baseline to Time of Event (Up to Approximately 6 Years)

    Outcome Measure Data

    Analysis Population Description
    ITT population: All randomized participants received at least one dose of drug and completed the follow up period
    Arm/Group Title Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SIDE
    Arm/Group Description Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe. Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by participants who were willing and judged competent by the HCP.
    Measure Participants 1865 708
    0.5 Year
    0.999
    0.996
    1 Year
    0.998
    0.994
    1.5 Year
    0.993
    0.990
    2 Years
    0.985
    0.985
    3 Years
    0.968
    0.960
    4 Years
    0.947
    0.950
    5 Years
    0.937
    0.929
    6 Years
    0.927
    0.921
    12. Secondary Outcome
    Title Percentage of Participants by Item Response to SID Satisfaction Questionnaire
    Description The SID satisfaction questionnaire was administered twice during the study and asked participants to respond to five statements using a Likert scale from "Strongly Disagree" to "Strongly Agree". Questionnaire items were as follows: "I felt comfortable injecting the study drug by myself" (Comfortable), "The SID was convenient and easy to use" (Easy to Use), "I am confident giving myself an injection in the thigh with the SID" (Confident), "Taking all things into account I find self-administration using the SID satisfactory" (Satisfactory), "If given the opportunity I would choose to continue self-injecting the study drug using the SID in the future" (Continue). Participants could only select one response per questionnaire item. There was no calculation of any score, but rather, descriptive summaries were generated by item response. The percentage of participants was reported by the response given for each item on the SID satisfaction questionnaire.
    Time Frame Cycle 4 (cycle length 3 weeks) and last safety follow-up (LSFU) (approximately 1 year)

    Outcome Measure Data

    Analysis Population Description
    Safety Population. Only participants who performed self-administration were included. The number of participants who responded to the questionnaire item at each assessment (n) is shown in the table.
    Arm/Group Title Cohort B: SC Herceptin by SID (Self- Administered)
    Arm/Group Description Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. Dosing was either performed by self-administration or a qualified HCP. The present subgroup included only participants for whom SC Herceptin was given by self- administration.
    Measure Participants 550
    Cycle 4: Comfortable, Strongly Disagree (n=514)
    4.7
    0.3%
    Cycle 4: Comfortable, Disagree (n=514)
    2.3
    0.1%
    Cycle 4: Comfortable, Unsure (n=514)
    7.6
    0.4%
    Cycle 4: Comfortable, Agree (n=514)
    41.6
    2.2%
    Cycle 4: Comfortable, Strongly Agree (n=514)
    43.6
    2.3%
    Cycle 4: Comfortable, Response Missing (n=514)
    0.2
    0%
    Cycle 4: Easy to Use, Strongly Disagree (n=514)
    3.7
    0.2%
    Cycle 4: Easy to Use, Disagree (n=514)
    0.6
    0%
    Cycle 4: Easy to Use, Unsure (n=514)
    1.8
    0.1%
    Cycle 4: Easy to Use, Agree (n=514)
    37.7
    2%
    Cycle 4: Easy to Use, Strongly Agree (n=514)
    56.0
    3%
    Cycle 4: Easy to Use, Response Missing (n=514)
    0.2
    0%
    Cycle 4: Confident, Strongly Disagree (n=514)
    3.9
    0.2%
    Cycle 4: Confident, Disagree (n=514)
    0.8
    0%
    Cycle 4: Confident, Unsure (n=514)
    7.2
    0.4%
    Cycle 4: Confident, Agree (n=514)
    42.8
    2.3%
    Cycle 4: Confident, Strongly Agree (n=514)
    45.1
    2.4%
    Cycle 4: Confident, Response Missing (n=514)
    0.2
    0%
    Cycle 4: Satisfactory, Strongly Disagree (n=514)
    3.9
    0.2%
    Cycle 4: Satisfactory, Disagree (n=514)
    0.6
    0%
    Cycle 4: Satisfactory, Unsure (n=514)
    2.7
    0.1%
    Cycle 4: Satisfactory, Agree (n=514)
    38.7
    2.1%
    Cycle 4: Satisfactory, Strongly Agree (n=514)
    53.9
    2.9%
    Cycle 4: Satisfactory, Response Missing (n=514)
    0.2
    0%
    Cycle 4: Continue, Strongly Disagree (n=514)
    3.9
    0.2%
    Cycle 4: Continue, Disagree (n=514)
    1.4
    0.1%
    Cycle 4: Continue, Unsure (n=514)
    5.3
    0.3%
    Cycle 4: Continue, Agree (n=514)
    33.5
    1.8%
    Cycle 4: Continue, Strongly Agree (n=514)
    55.8
    3%
    Cycle 4: Continue, Response Missing (n=514)
    0.2
    0%
    LSFU: Comfortable, Strongly Disagree (n=415)
    3.6
    0.2%
    LSFU: Comfortable, Disagree (n=415)
    3.1
    0.2%
    LSFU: Comfortable, Unsure (n=415)
    5.3
    0.3%
    LSFU: Comfortable, Agree (n=415)
    35.9
    1.9%
    LSFU: Comfortable, Strongly Agree (n=415)
    51.8
    2.8%
    LSFU: Comfortable, Response Missing (n=415)
    0.2
    0%
    LSFU: Easy to Use, Strongly Disagree (n=415)
    3.9
    0.2%
    LSFU: Easy to Use, Disagree (n=415)
    1.0
    0.1%
    LSFU: Easy to Use, Unsure (n=415)
    1.7
    0.1%
    LSFU: Easy to Use, Agree (n=415)
    34.9
    1.9%
    LSFU: Easy to Use, Strongly Agree (n=415)
    58.6
    3.1%
    LSFU: Easy to Use, Response Missing (n=415)
    0
    0%
    LSFU: Confident, Strongly Disagree (n=415)
    4.6
    0.2%
    LSFU: Confident, Disagree (n=415)
    1.2
    0.1%
    LSFU: Confident, Unsure (n=415)
    4.3
    0.2%
    LSFU: Confident, Agree (n=415)
    33.3
    1.8%
    LSFU: Confident, Strongly Agree (n=415)
    56.6
    3%
    LSFU: Confident, Response Missing (n=415)
    0
    0%
    LSFU: Satisfactory, Strongly Disagree (n=415)
    4.3
    0.2%
    LSFU: Satisfactory, Disagree (n=415)
    1.2
    0.1%
    LSFU: Satisfactory, Unsure (n=415)
    2.2
    0.1%
    LSFU: Satisfactory, Agree (n=415)
    30.8
    1.6%
    LSFU: Satisfactory, Strongly Agree (n=415)
    61.2
    3.3%
    LSFU: Satisfactory, Response Missing (n=415)
    0.2
    0%
    LSFU: Continue, Strongly Disagree (n=415)
    4.6
    0.2%
    LSFU: Continue, Disagree (n=415)
    1.2
    0.1%
    LSFU: Continue, Unsure (n=415)
    2.9
    0.2%
    LSFU: Continue, Agree (n=415)
    28.2
    1.5%
    LSFU: Continue, Strongly Agree (n=415)
    63.1
    3.4%
    LSFU: Continue, Response Missing (n=415)
    0
    0%

    Adverse Events

    Time Frame Treatment Period: From Day 1 up to 19 cycles (approximately 1 year) 15 March 2015 Data Cutoff Safety Follow-up Period (SFU): From Day 1 to safety follow-up period (up to approximately 8 years)
    Adverse Event Reporting Description Safety Population. During the Safety Follow-up Period, no non-Serious Adverse Events occurred at the 5% frequency threshold. In the Safety Follow-up period, 4 participants were not included in the final analyses due to the lack of Principal Investigator signatures in the participant specific casebooks.
    Arm/Group Title Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SID Cohort A: SC Herceptin by Needle/Syringe Safety Follow-up Cohort B: SC Herceptin by SID Safety Follow-up
    Arm/Group Description Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe. Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by participants who were willing and judged competent by the HCP. Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe. Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by participants who were willing and judged competent by the HCP.
    All Cause Mortality
    Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SID Cohort A: SC Herceptin by Needle/Syringe Safety Follow-up Cohort B: SC Herceptin by SID Safety Follow-up
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SID Cohort A: SC Herceptin by Needle/Syringe Safety Follow-up Cohort B: SC Herceptin by SID Safety Follow-up
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 242/1864 (13%) 84/709 (11.8%) 202/1862 (10.8%) 53/707 (7.5%)
    Blood and lymphatic system disorders
    Febrile neutropenia 39/1864 (2.1%) 14/709 (2%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Neutropenia 9/1864 (0.5%) 6/709 (0.8%) 0/1862 (0%) 0/707 (0%)
    Febrile bone marrow aplasia 2/1864 (0.1%) 2/709 (0.3%) 0/1862 (0%) 0/707 (0%)
    Anaemia 3/1864 (0.2%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Leukocytosis 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Leukopenia 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Pancytopenia 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Thymus enlargement 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Lymphadenopathy 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Thrombocytopenia 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Cardiac disorders
    Cardiac failure congestive 10/1864 (0.5%) 1/709 (0.1%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Atrial fibrillation 2/1864 (0.1%) 0/709 (0%) 6/1862 (0.3%) 6 0/707 (0%) 6
    Angina unstable 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Coronary artery disease 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Left ventricular dysfunction 1/1864 (0.1%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Myocardial ischaemia 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Pericarditis 1/1864 (0.1%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Supraventricular tachycardia 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Acute myocardial infarction 1/1864 (0.1%) 0/709 (0%) 3/1862 (0.2%) 3 1/707 (0.1%) 1
    Atrial thrombosis 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Atrioventricular block second degree 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Myocarditis 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Palpitations 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%)
    Stress cardiomyopathy 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Ventricular arrhythmia 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Myocardial Infarction 0/1864 (0%) 0/709 (0%) 6/1862 (0.3%) 6 0/707 (0%) 6
    Acute Coronary Syndrome 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Angina Pectoris 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Arteriosclerosis Coronary Artery 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Atrial Flutter 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Atrial Tachycardia 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Cardiac Hypertrophy 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Cardio-Respiratory Arrest 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Tachycardia 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Intracardiac Thrombus 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Ear and labyrinth disorders
    Vertigo 2/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 1 1/707 (0.1%) 1
    Meniere's disease 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0 0/707 (0%) 0
    Endocrine disorders
    Hypothyroidism 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0 0/707 (0%) 0
    Thyroiditis Subacute 0/1864 (0%) 0 0/709 (0%) 0 1/1862 (0.1%) 1 0/707 (0%) 0
    Eye disorders
    Keratitis 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Gastrointestinal disorders
    Diarrhoea 8/1864 (0.4%) 4/709 (0.6%) 0/1862 (0%) 0/707 (0%)
    Nausea 5/1864 (0.3%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Pancreatitis 3/1864 (0.2%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Abdominal pain upper 1/1864 (0.1%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Pancreatitis acute 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Vomiting 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Abdominal pain 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Abdominal discomfort 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Colitis 1/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Constipation 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Gastritis erosive 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Gastrointestinal pain 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Intestinal polyp 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Neutropenic colitis 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Subileus 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Anal Fissure 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Diverticulum Intestinal 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Food Poisoning 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Gastritis 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Hiatus Hernia 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Intestinal Obstruction 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Small Intestinal Obstruction 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Upper Gastrointestinal Haemorrhage 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Inguinal Hernia 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    General disorders
    Pyrexia 11/1864 (0.6%) 7/709 (1%) 1/1862 (0.1%) 1 1/707 (0.1%) 1
    General physical health deterioration 1/1864 (0.1%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Asthenia 1/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Chest discomfort 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Chest pain 1/1864 (0.1%) 0/709 (0%) 2/1862 (0.1%) 2 0/707 (0%) 0
    Death 0/1864 (0%) 1/709 (0.1%) 6/1862 (0.3%) 6 1/707 (0.1%) 1
    Device defective 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Fatigue 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Influenza like illness 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Mucosal inflammation 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Non- cardiac chest pain 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Oedema peripheral 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Sudden Death 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Hepatobiliary disorders
    Cholelithiasis 2/1864 (0.1%) 1/709 (0.1%) 3/1862 (0.2%) 3 2/707 (0.3%) 2
    Cholecystitis chronic 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Bile Duct Obstruction 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Bile Duct Stenosis 0/1864 (0%) 0 0/709 (0%) 0 1/1862 (0.1%) 1 0/707 (0%) 0
    Cholangitis Acute 0/1864 (0%) 0 0/709 (0%) 0 1/1862 (0.1%) 1 0/707 (0%) 0
    Hepatic Failure 0/1864 (0%) 0 0/709 (0%) 0 1/1862 (0.1%) 1 1/707 (0.1%) 1
    Hepatic Steatosis 0/1864 (0%) 0 0/709 (0%) 0 1/1862 (0.1%) 1 1/707 (0.1%) 1
    Acute Hepatic Failure 0/1864 (0%) 0 0/709 (0%) 0 0/1862 (0%) 0 1/707 (0.1%) 1
    Cholecystitis 0/1864 (0%) 0 0/709 (0%) 0 1/1862 (0.1%) 1 1/707 (0.1%) 1
    Immune system disorders
    Drug hypersensitivity 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Hypersensitivity 0/1864 (0%) 2/709 (0.3%) 0/1862 (0%) 0/707 (0%)
    Anaphylactic Shock 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 1/707 (0.1%) 1
    Infections and infestations
    Neutropenic sepsis 9/1864 (0.5%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Device related infection 6/1864 (0.3%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Pneumonia 5/1864 (0.3%) 5 1/709 (0.1%) 5 8/1862 (0.4%) 8 2/707 (0.3%) 2
    Urinary tract infection 3/1864 (0.2%) 2/709 (0.3%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Mastitis 3/1864 (0.2%) 2/709 (0.3%) 4/1862 (0.2%) 4 0/707 (0%) 0
    Cellulitis 4/1864 (0.2%) 0/709 (0%) 4/1862 (0.2%) 4 1/707 (0.1%) 1
    Gastroenteritis 3/1864 (0.2%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%) 0
    Lower respiratory tract infection 4/1864 (0.2%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Appendicitis 2/1864 (0.1%) 1/709 (0.1%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Upper respiratory tract infection 2/1864 (0.1%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Breast abscess 2/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Erysipelas 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Infectious colitis 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Pyelonephritis acute 2/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Viral infection 1/1864 (0.1%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Infective exacerbation of chronic obstructive airways disease 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Abscess of external auditory meatus 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Appendiceal abscess 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Bartholin's abscess 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Breast cellulitis 0/1864 (0%) 1/709 (0.1%) 2/1862 (0.1%) 2 0/707 (0%) 0
    Bronchitis 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Bronchopneumonia 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Clostridium difficile infection 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Dengue fever 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Diverticulitis 1/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Febrile infection 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Gastroenteritis rotavirus 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Hepatitis B 0/1864 (0%) 1/709 (0.1%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Herpes zoster 1/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Intestinal sepsis 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Lobar pneumonia 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Localised infection 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Lung infection 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Lymph node tuberculosis 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Meningoencephalitis bacterial 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Periorbital cellulitis 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Pneumonia bacterial 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Postoperative wound infection 1/1864 (0.1%) 0/709 (0%) 2/1862 (0.1%) 2 0/707 (0%) 2
    Pyelonephritis 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Respiratory tract infection 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Skin infection 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Soft tissue infection 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Staphylococcal infection 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Tracheobronchitis 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Urosepsis 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Vaginal infection 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Wound infection 0/1864 (0%) 1/709 (0.1%) 2/1862 (0.1%) 2 0/707 (0%) 2
    Escherichia Sepsis 0/1864 (0%) 0/709 (0%) 2/1862 (0.1%) 2 0/707 (0%) 2
    Infection 0/1864 (0%) 0/709 (0%) 2/1862 (0.1%) 2 0/707 (0%) 2
    Biliary Tract Infection 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Chronic Sinusitis 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Dengue Haemorrhagic Fever 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Diabetic Gangrene 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Endocarditis 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Enterobacter Sepsis 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Gastroenteritis Viral 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Kidney Infection 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Post Procedural Cellulitis 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Pulmonary Sepsis 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Sepsis 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Pneumonia Influenzal 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Pneumonia Streptococcal 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Injury, poisoning and procedural complications
    Radiation pneumonitis 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Hip fracture 1/1864 (0.1%) 1/709 (0.1%) 1/1862 (0.1%) 1 1/707 (0.1%) 1
    Wound dehiscence 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 1/707 (0.1%) 1
    Concussion 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Fibula fracture 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Fracture displacement 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Laceration 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Lumbar vertebral fracture 1/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Patella fracture 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Pelvic fracture 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Radius fracture 1/1864 (0.1%) 0/709 (0%) 2/1862 (0.1%) 0/707 (0%)
    Seroma 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Spinal fracture 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Tibia fracture 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Traumatic arthropathy 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Ulna fracture 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Wound 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Fall 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 2/707 (0.3%) 2
    Foot Fracture 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Foreign Body Aspiration 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Lower Limb Fracture 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 1/707 (0.1%) 1
    Pubis Fracture 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Ankle Fracture 0/1864 (0%) 0/709 (0%) 3/1862 (0.2%) 3 0/707 (0%) 3
    Femoral Neck Fracture 0/1864 (0%) 0/709 (0%) 3/1862 (0.2%) 3 0/707 (0%) 3
    Clavicle Fracture 0/1864 (0%) 0/709 (0%) 2/1862 (0.1%) 2 0/707 (0%) 2
    Humerus Fracture 0/1864 (0%) 0/709 (0%) 2/1862 (0.1%) 2 0/707 (0%) 2
    Rib Fracture 0/1864 (0%) 0/709 (0%) 2/1862 (0.1%) 2 0/707 (0%) 2
    Spinal Compression Fracture 0/1864 (0%) 0/709 (0%) 2/1862 (0.1%) 2 0/707 (0%) 2
    Intentional Overdose 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 2 0/707 (0%) 2
    Craniocerebral Injury 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Fracture 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Head Injury 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Incisional Hernia 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Joint Dislocation 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Post Procedural Haematoma 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Thoracic Vertebral Fracture 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Wrist Fracture 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Investigations
    Ejection fraction decreased 3/1864 (0.2%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 0
    White blood cell count decreased 1/1864 (0.1%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Blood urea increased 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Electrocardiogram QT prolonged 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Neutrophil count decreased 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Metabolism and nutrition disorders
    Hyperglycaemia 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Electrolyte imbalance 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Gout 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Hypokalaemia 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Hyponatraemia 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Decreased Appetite 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 1/707 (0.1%) 1
    Diabetes Mellitus 0/1864 (0%) 0 0/709 (0%) 0 1/1862 (0.1%) 1 0/707 (0%) 0
    Hyperkalaemia 0/1864 (0%) 0 0/709 (0%) 0 0/1862 (0%) 0 1/707 (0.1%) 1
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 2/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 1 1/707 (0.1%) 1
    Arthritis 1/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Intervertebral disc protrusion 1/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 1 1/707 (0.1%) 1
    Lumbar spinal stenosis 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Myalgia 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Rheumatoid arthritis 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Arthralgia 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Exostosis 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Mobility Decreased 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Musculoskeletal Disorder 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Scleroderma 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Spinal Stenosis 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma 1/1864 (0.1%) 2/709 (0.3%) 0/1862 (0%) 0/707 (0%)
    Benign pancreatic neoplasm 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Borderline serous tumour of ovary 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Breast cancer 1/1864 (0.1%) 0/709 (0%) 15/1862 (0.8%) 15 1/707 (0.1%) 1
    Clear cell renal cell carcinoma 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Colon cancer 0/1864 (0%) 1/709 (0.1%) 2/1862 (0.1%) 0/707 (0%)
    Endometrial cancer 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Intraductal proliferative breast lesion 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Lung adenocarcinoma 0/1864 (0%) 1/709 (0.1%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Ovarian fibroma 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Rectal adenocarcinoma 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Schwannoma 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Thyroid adenoma 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Papillary Thyroid Cancer 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Uterine Cancer 0/1864 (0%) 0/709 (0%) 2/1862 (0.1%) 2 1/707 (0.1%) 1
    Ovarian Cancer Recurrent 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Ovarian Cancer 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 1/707 (0.1%) 1
    Metastatic Gastric Cancer 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 1/707 (0.1%) 1
    Lung Neoplasm Malignant 0/1864 (0%) 0/709 (0%) 2/1862 (0.1%) 2 1/707 (0.1%) 1
    Lung Cancer Metastatic 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Gastrointestinal Carcinoma 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Gastric Cancer 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Adenocarcinoma of Colon 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 1/707 (0.1%) 1
    Lymphocytic Lymphoma 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Invasive Lobular Breast Carcinoma 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Invasive Ductal Breast Carcinoma 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Hepatocellular Carcinoma 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Glioma 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Glioblastoma 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Endometrial Adenocarcinoma 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Colon Cancer Metastatic 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Chondroma 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Breast Sarcoma 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Breast Neoplasm 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Bladder Cancer 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Basal Cell Carcinoma 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Synovial Sarcoma Metastatic 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 2 0/707 (0%) 2
    Malignant Melanoma 0/1864 (0%) 0/709 (0%) 3/1862 (0.2%) 3 0/707 (0%) 3
    Vulval Cancer 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Thyroid Cancer 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Renal Cell Carcinoma 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Pancreatic Carcinoma 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Ovarian Epithelial Cancer Metastatic 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Non-Hodgkin's Lymphoma 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Nervous system disorders
    Headache 2/1864 (0.1%) 0/709 (0%) 2/1862 (0.1%) 2 0/707 (0%) 2
    Syncope 1/1864 (0.1%) 1/709 (0.1%) 2/1862 (0.1%) 3 0/707 (0%) 3
    Aphasia 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Carotid sinus syndrome 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Cerebral ischaemia 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Cerebrovascular accident 1/1864 (0.1%) 0/709 (0%) 2/1862 (0.1%) 2 2/707 (0.3%) 2
    Depressed level of consciousness 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Epilepsy 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Generalised tonic-clonic seizure 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Peripheral sensorimotor neuropathy 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Presyncope 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Tension headache 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Transient ischaemic attack 1/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 2 1/707 (0.1%) 1
    Cerebral Infarction 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Dementia 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Dementia Alzheimer's Type 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Relapsing-Remitting Multiple Sclerosis 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Seizure 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Amyotrophic Lateral Sclerosis 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Cerebral Haemorrhage 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Cerebrovascular Disorder 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Haemorrhagic Stroke 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Dizziness 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Hydrocephalus 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Sciatica 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Pregnancy, puerperium and perinatal conditions
    Anembryonic Gestation 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Product Issues
    Device breakage 1/1864 (0.1%) 1/709 (0.1%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Psychiatric disorders
    Anxiety 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Depression 1/1864 (0.1%) 1/709 (0.1%) 2/1862 (0.1%) 2 0/707 (0%) 0
    Panic attack 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Psychotic disorder 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Renal and urinary disorders
    Renal failure 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Hydronephrosis 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Urinary incontinence 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Urinary retention 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Acute Kidney Injury 0/1864 (0%) 0 0/709 (0%) 0 2/1862 (0.1%) 2 0/707 (0%) 0
    Renal Colic 0/1864 (0%) 0 0/709 (0%) 0 2/1862 (0.1%) 2 0/707 (0%) 0
    Haematuria 0/1864 (0%) 0 0/709 (0%) 0 1/1862 (0.1%) 1 0/707 (0%) 0
    Nephrolithiasis 0/1864 (0%) 0 0/709 (0%) 0 1/1862 (0.1%) 1 0/707 (0%) 0
    Nephrotic Syndrome 0/1864 (0%) 0 0/709 (0%) 0 1/1862 (0.1%) 1 0/707 (0%) 0
    Urinary Bladder Polyp 0/1864 (0%) 0 0/709 (0%) 0 1/1862 (0.1%) 1 0/707 (0%) 0
    Reproductive system and breast disorders
    Uterine polyp 2/1864 (0.1%) 2 0/709 (0%) 0 3/1862 (0.2%) 3 0/707 (0%) 0
    Breast fibrosis 1/1864 (0.1%) 1 0/709 (0%) 0 0/1862 (0%) 0 1/707 (0.1%) 1
    Endometrial hypertrophy 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Ovarian cyst 1/1864 (0.1%) 0/709 (0%) 2/1862 (0.1%) 2 1/707 (0.1%) 1
    Postmenopausal haemorrhage 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Uterine haemorrhage 1/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Endometrial Hyperplasia 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Breast Necrosis 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 1/707 (0.1%) 1
    Cervical Dysplasia 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Fibrocystic Breast Disease 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Vaginal Haemorrhage 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Breast Calcifications 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Respiratory, thoracic and mediastinal disorders
    Asthma 2/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Dyspnoea 2/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Pneumonitis 1/1864 (0.1%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Pulmonary embolism 0/1864 (0%) 2/709 (0.3%) 4/1862 (0.2%) 4 1/707 (0.1%) 1
    Dyspnoea exertional 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Organising pneumonia 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Painful respiration 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Pleurisy 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Pulmonary oedema 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Respiratory failure 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Pleural Effusion 0/1864 (0%) 0/709 (0%) 2/1862 (0.1%) 2 0/707 (0%) 2
    Epistaxis 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Pulmonary Sarcoidosis 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Chronic Obstructive Pulmonary Disease 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Obstructive Airways Disorder 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 2
    Skin and subcutaneous tissue disorders
    Dermatitis 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Dermatitis bullous 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Erythema nodosum 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Rash 1/1864 (0.1%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Toxic skin eruption 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Transient acantholytic dermatosis 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Erythema 0/1864 (0%) 0/709 (0%) 2/1862 (0.1%) 2 0/707 (0%) 0
    Lichen Sclerosus 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Vascular disorders
    Hypertension 2/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Hypertensive crisis 1/1864 (0.1%) 1/709 (0.1%) 2/1862 (0.1%) 2 0/707 (0%) 2
    Aortic aneurysm 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Arterial stenosis 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Deep vein thrombosis 0/1864 (0%) 1/709 (0.1%) 1/1862 (0.1%) 1 0/707 (0%) 0
    Orthostatic hypotension 0/1864 (0%) 1/709 (0.1%) 0/1862 (0%) 0/707 (0%)
    Phlebitis 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Venous thrombosis 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Venous thrombosis limb 1/1864 (0.1%) 0/709 (0%) 0/1862 (0%) 0/707 (0%)
    Thromboangiitis Obliterans 0/1864 (0%) 0/709 (0%) 0/1862 (0%) 1/707 (0.1%) 1
    Varicose Vein 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 0/707 (0%)
    Hypertensive Urgency 0/1864 (0%) 0/709 (0%) 1/1862 (0.1%) 1 0/707 (0%) 1
    Other (Not Including Serious) Adverse Events
    Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by SID Cohort A: SC Herceptin by Needle/Syringe Safety Follow-up Cohort B: SC Herceptin by SID Safety Follow-up
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1499/1864 (80.4%) 576/709 (81.2%) 0/1862 (0%) 0/707 (0%)
    Blood and lymphatic system disorders
    Anaemia 130/1864 (7%) 43/709 (6.1%) 0/1862 (0%) 0/707 (0%)
    Neutropenia 101/1864 (5.4%) 36/709 (5.1%) 0/1862 (0%) 0/707 (0%)
    Gastrointestinal disorders
    Diarrhoea 380/1864 (20.4%) 130/709 (18.3%) 0/1862 (0%) 0/707 (0%)
    Nausea 274/1864 (14.7%) 102/709 (14.4%) 0/1862 (0%) 0/707 (0%)
    Constipation 153/1864 (8.2%) 62/709 (8.7%) 0/1862 (0%) 0/707 (0%)
    Vomiting 129/1864 (6.9%) 38/709 (5.4%) 0/1862 (0%) 0/707 (0%)
    Stomatitis 116/1864 (6.2%) 42/709 (5.9%) 0/1862 (0%) 0/707 (0%)
    Abdominal pain 87/1864 (4.7%) 36/709 (5.1%) 0/1862 (0%) 0/707 (0%)
    Dyspepsia 69/1864 (3.7%) 44/709 (6.2%) 0/1862 (0%) 0/707 (0%)
    General disorders
    Fatigue 381/1864 (20.4%) 132/709 (18.6%) 0/1862 (0%) 0/707 (0%)
    Asthenia 221/1864 (11.9%) 85/709 (12%) 0/1862 (0%) 0/707 (0%)
    Pyrexia 185/1864 (9.9%) 55/709 (7.8%) 0/1862 (0%) 0/707 (0%)
    Oedema peripheral 160/1864 (8.6%) 45/709 (6.3%) 0/1862 (0%) 0/707 (0%)
    Injection site erythema 128/1864 (6.9%) 52/709 (7.3%) 0/1862 (0%) 0/707 (0%)
    Mucosal inflammation 105/1864 (5.6%) 53/709 (7.5%) 0/1862 (0%) 0/707 (0%)
    Injection site pain 117/1864 (6.3%) 37/709 (5.2%) 0/1862 (0%) 0/707 (0%)
    Injection site reaction 101/1864 (5.4%) 36/709 (5.1%) 0/1862 (0%) 0/707 (0%)
    Pain 63/1864 (3.4%) 36/709 (5.1%) 0/1862 (0%) 0/707 (0%)
    Infections and infestations
    Nasopharyngitis 146/1864 (7.8%) 58/709 (8.2%) 0/1862 (0%) 0/707 (0%)
    Upper respiratory tract infection 113/1864 (6.1%) 21/709 (3%) 0/1862 (0%) 0/707 (0%)
    Urinary tract infection 94/1864 (5%) 32/709 (4.5%) 0/1862 (0%) 0/707 (0%)
    Injury, poisoning and procedural complications
    Radiation skin injury 161/1864 (8.6%) 68/709 (9.6%) 0/1862 (0%) 0/707 (0%)
    Investigations
    Ejection fraction decreased 80/1864 (4.3%) 36/709 (5.1%) 0/1862 (0%) 0/707 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 362/1864 (19.4%) 133/709 (18.8%) 0/1862 (0%) 0/707 (0%)
    Myalgia 260/1864 (13.9%) 84/709 (11.8%) 0/1862 (0%) 0/707 (0%)
    Pain in extremity 194/1864 (10.4%) 49/709 (6.9%) 0/1862 (0%) 0/707 (0%)
    Back pain 114/1864 (6.1%) 42/709 (5.9%) 0/1862 (0%) 0/707 (0%)
    Musculoskeletal pain 89/1864 (4.8%) 36/709 (5.1%) 0/1862 (0%) 0/707 (0%)
    Bone pain 70/1864 (3.8%) 40/709 (5.6%) 0/1862 (0%) 0/707 (0%)
    Nervous system disorders
    Headache 228/1864 (12.2%) 73/709 (10.3%) 0/1862 (0%) 0/707 (0%)
    Neuropathy peripheral 140/1864 (7.5%) 56/709 (7.9%) 0/1862 (0%) 0/707 (0%)
    Paraesthesia 112/1864 (6%) 70/709 (9.9%) 0/1862 (0%) 0/707 (0%)
    Dizziness 111/1864 (6%) 32/709 (4.5%) 0/1862 (0%) 0 0/707 (0%) 0
    Peripheral sensory neuropathy 94/1864 (5%) 21/709 (3%) 0/1862 (0%) 0/707 (0%)
    Psychiatric disorders
    Insomnia 108/1864 (5.8%) 50/709 (7.1%) 0/1862 (0%) 0/707 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 190/1864 (10.2%) 56/709 (7.9%) 0/1862 (0%) 0/707 (0%)
    Dyspnoea 115/1864 (6.2%) 47/709 (6.6%) 0/1862 (0%) 0/707 (0%)
    Epistaxis 109/1864 (5.8%) 30/709 (4.2%) 0/1862 (0%) 0/707 (0%)
    Skin and subcutaneous tissue disorders
    Rash 177/1864 (9.5%) 74/709 (10.4%) 0/1862 (0%) 0/707 (0%)
    Erythema 156/1864 (8.4%) 74/709 (10.4%) 0/1862 (0%) 0/707 (0%)
    Alopecia 163/1864 (8.7%) 49/709 (6.9%) 0/1862 (0%) 0/707 (0%)
    Pruritus 115/1864 (6.2%) 35/709 (4.9%) 0/1862 (0%) 0/707 (0%)
    Vascular disorders
    Hot flush 164/1864 (8.8%) 72/709 (10.2%) 0/1862 (0%) 0/707 (0%)
    Hypertension 142/1864 (7.6%) 35/709 (4.9%) 0/1862 (0%) 0/707 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

    Results Point of Contact

    Name/Title Medical Communications
    Organization Hoffmann-La Roche
    Phone 800-821-8590
    Email global-roche-genentech-trials@gene.com
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT01566721
    Other Study ID Numbers:
    • MO28048
    • 2011-005328-17
    First Posted:
    Mar 29, 2012
    Last Update Posted:
    Apr 27, 2021
    Last Verified:
    Apr 1, 2021