A Study of Neoadjuvant Letrozole + Taselisib Versus Letrozole + Placebo in Post-Menopausal Women With Breast Cancer (LORELEI)

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02273973
• Collaborator: SOLTI Breast Cancer Research Group (Other), Breast International Group (Other), Austrian Breast and Colorectal Cancer Group (Other)
• Enrollment: 334
• Locations: 117
• Arms: 2
• Actual Duration (Months): 28
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a two-arm, randomized, double-blind, multicenter, pre-operative study to evaluate the effect of combining letrozole and GDC-0032 (also known as taselisib) versus letrozole and placebo in postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2 (HER2) untreated, Stage I-III operable breast cancer. Participants will be randomized into one of the two treatment arms with a 1:1 randomization ratio. Letrozole at 2.5 milligrams (mg) will be dosed once daily plus either Taselisib at 4 mg (two 2-mg tablets) or placebo on a 5 days-on/ 2 days-off schedule for a total of 16 weeks.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Letrozole; Other: Placebo; Drug: Taselisib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 334 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized, Double-Blind Study of Neoadjuvant Letrozole Plus GDC-0032 Versus Letrozole Plus Placebo in Postmenopausal Women With ER-positive/HER2-negative, Early Stage Breast Cancer
• Actual Study Start Date: Nov 12, 2014
• Actual Primary Completion Date: Mar 13, 2017
• Actual Study Completion Date: Mar 13, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Letrozole + Placebo Participants will receive 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.	Drug: Letrozole; Letrozole tablets will be administered orally at 2.5 mg QD for 16 weeks.; Other: Placebo; Placebo tablets matched to taselisib formulation will be administered orally daily on 5 days-on/2 days-off schedule for up to 16 weeks.
Experimental: Letrozole + Taselisib Participants will receive 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Drug: Letrozole; Letrozole tablets will be administered orally at 2.5 mg QD for 16 weeks.; Drug: Taselisib; Taselisib will be administered orally at 4 mg (two 2 mg tablets) daily.; Other Names: GDC-0032

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Objective Response (OR) by Centrally Assessed Breast Magnetic Resonance Imaging (MRI) Via Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Version 1.1 [From Baseline to 16 weeks]

   Objective response rate (ORR) was defined as proportion of participants achieving complete response (CR) or partial response (PR). As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

2. Percentage of Participants With Total Pathologic Complete Response (Total pCR), Defined as Having pCR in Both Breast and Axilla, Using American Joint Committee on Cancer (AJCC) Staging System [From Baseline to 16 weeks]

   Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes ( i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).

3. Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in Phosphatidylinositol-4,5-Bisphosphate 3-Kinase, Catalytic Subunit Alpha (PIK3CA) Mutant (MT) Participants [From Baseline to 16 weeks]

   ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

4. Percentage of Participants With Total pCR , Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA MT Participants [From Baseline to 16 weeks]

   Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes (i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).

Secondary Outcome Measures

1. Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in PIK3CA Wildtype (WT) Participants [From Baseline to 16 weeks]

   ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

2. Percentage of Participants With Total pCR Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA WT Participants [From Baseline to 16 weeks]

   Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes (i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).

3. Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA MT Participants [From Baseline to 16 weeks]

   ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

4. Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA WT Participants [From Baseline to 16 weeks]

   ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

5. Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA MT Participants [From Baseline to 16 weeks]

   ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

6. Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA WT Participants [From Baseline to 16 weeks]

   ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

7. Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA MT Participants [From Baseline to 16 weeks]

   ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

8. Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA WT Participants [From Baseline to 16 weeks]

   ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

9. Central Assessments of Changes in Ki67 Levels [From Baseline to Week 3 and Surgery (Weeks 17-18); and Week 3 to Surgery (Weeks 17-18)]

   Ki67 is a prognostic marker and is used to evaluate the proliferative activity of breast cancer.

10. Preoperative Endocrine Prognostic Index (PEPI ) Score [Week 16]

    To obtain the PEPI score, risk points for relapse-free survival (RFS) and breast cancer-specific survival (BCSS) are assigned depending on the hazard ratio (HR) from the multivariable analysis. The total PEPI score assigned to each participant is the sum of the risk points derived from the primary tumor (pT) stage, regional lymph nodes (pN) stage, Ki67 level, and estrogen receptor status of the surgical specimen. A HR in the range of 1 to 2 receives one risk point; a HR in the 2 to 2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each participant is the sum of all the risk points accumulated from the four factors in the model, ranges from 0 (best possible outcome) to 12 (worst possible outcome).

11. Percent Change From Baseline to Surgery in Enhancing Tumor Volume as Measured by Breast MRI [From Baseline to Surgery (Weeks 17-18)]

12. Mean Score for Health-Related Quality of Life Measured by the European Organization for Research C30 (EORTC QLQ-C30) [Weeks 1, 5, 9, 13, 16, 4-week Post-Surgery]

    EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall quality of life (QOL) in cancer participants. The first 28 questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting [N/V], constipation, and pain) and a single item (financial difficulties). The last 2 questions represented the participant's assessment of overall health and quality of life, used 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 global scores were linearly transformed on a scale of 0 to 100, with a high score indicating better QOL. Negative change from Baseline values indicated deterioration in QOL or functioning and positive values indicated improvement. Here, Post surgery= PS.

13. Mean Score for Treatment of Cancer Quality of Life Questionnaire BR23 (QLQ-BR23) [Weeks 1, 5, 9, 13, 16, 4-week Post-Surgery]

    EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL. Here, Post surgery= PS.

14. Percentage of Participants With Adverse Events [Baseline up to 22 weeks]

    An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Female participants

• Postmenopausal status

• Histologically confirmed invasive breast carcinoma, with all of the following characteristics: (i) Primary tumor greater than or equal to (>/=) 2 centimeters (cm) in largest diameter (cT1-3) by MRI; (ii) Stage I to operable Stage III breast cancer; (iii) Documented absence of distant metastases (M0)

• Estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer

• Breast cancer eligible for primary surgery

• Tumor tissue from formalin-fixed paraffin-embedded cores (FFPE) core biopsy of breast primary tumor that is confirmed as evaluable for phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation status by central histopathology laboratory

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

• Fasting glucose less than or equal to (</=) 125 milligrams per deciliter (mg/dL)

• Adequate hematological, renal, and hepatic function

• Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

• Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol, in the investigator's judgment

Exclusion Criteria:

• Any prior treatment for primary invasive breast cancer

• Participants with cT4 or cN3 stage breast tumors

• Bilateral invasive, multicentric, or metastatic breast cancer

• Participants who have undergone excisional biopsy of primary tumor and/or axillary lymph nodes or sentinel lymph node biopsy

• Type 1 or 2 diabetes requiring antihyperglycemic medication

• Inability or unwillingness to swallow pills

• Malabsorption syndrome or other condition that would interfere with enteric absorption

• History of prior or currently active small or large intestine inflammation (such as Crohn's disease or ulcerative colitis). Any predisposition for gastrointestinal (GI) toxicity requires prior approval from the Medical Monitor.

• Congenital long QT syndrome or QT interval corrected using Fridericia's formula (QTcF)

470 milliseconds (msec)

• Diffusing capacity of the lungs for carbon monoxide (DLCO) <60% of the predicted values

• Clinically significant (i.e., active) cardiovascular disease, uncontrolled hypertension, unstable angina, history of myocardial infarction, cardiac failure class II-IV

• Any contraindication to MRI examination

• Active infection requiring intravenous antibiotics

• Participants requiring any daily supplemental oxygen

• Clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis

• Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or renders the participants at high risk from treatment complications

• Significant traumatic injury within 3 weeks prior to initiation of study treatment

• Major surgical procedure within 4 weeks prior to initiation of study treatment

• Inability to comply with study and follow-up procedures

• History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Breastlink Med Group Inc	Santa Ana	California	United States	92705
2	MGH Cancer Center	Boston	Massachusetts	United States	02114
3	MSKCC at Basking Ridge	Basking Ridge	New Jersey	United States	07920
4	MSKCC @ Commack	Commack	New York	United States	11725
5	MSKCC @ West Harrison	Harrison	New York	United States	10604
6	Memorial Sloan-Kettering Cancer Center; Hematology/Oncology	New York	New York	United States	10065
7	MSKC @ Rockville	Rockville Centre	New York	United States	11570
8	MD Anderson Cancer Center	Houston	Texas	United States	77030
9	Kinghorn Cancer Centre; St Vincents Hospital	Darlinghurst	New South Wales	Australia	2010
10	Newcastle Mater Misericordiae Hospital; Oncology	Waratah	New South Wales	Australia	2298
11	Victorian Breast and Oncology Care	East Melbourne	Victoria	Australia
12	Cabrini Medical Centre; Oncology	Malvern	Victoria	Australia	3144
13	Fiona Stanley Hospital	Murdoch	Western Australia	Australia	6150
14	Lkh-Univ. Klinikum Graz; Klinik Für Gynäkologie	Graz		Austria	8036
15	LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie	Graz		Austria	8036
16	Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie	Innsbruck		Austria	6020
17	Ordensklinikum Linz Barmherzige Schwestern ; Abt. f. Allgemein- und Viszeralchirurgie	Linz		Austria	4010
18	Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.	Salzburg		Austria	5020
19	Brustzentrum - Ordination Dr. Wette	St. Veit/Glan		Austria	9300
20	Klinikum Kreuzschwestern Wels; Iii. Interne Abt.	Wels		Austria	4600
21	Medizinische Universität Wien; Univ.Klinik für Chirurgie - Abt. für Allgemeinchirurgie	Wien		Austria	1090
22	Medizinische Universität Wien; Univ.Klinik für Frauenheilkunde - Klinik für Gynäkologie	Wien		Austria	1090
23	Krankenhaus Der Stadt Wien-Hietzing; Abt. Für Gynäkologie U. Geburtshilfe	Wien		Austria	1130
24	Institut Jules Bordet	Brussels		Belgium	1000
25	CHU Brugmann (Victor Horta)	Bruxelles		Belgium	1020
26	Cliniques Universitaires St-Luc	Bruxelles		Belgium	1200
27	UZ Antwerpen	Edegem		Belgium	2650
28	Clinique Ste-Elisabeth	Namur		Belgium	5000
29	Hospital Sao Lucas - PUCRS	Porto Alegre	RS	Brazil	90610-000
30	Clinica de Neoplasias Litoral	Itajai	SC	Brazil	88301-220
31	Hospital de Cancer de Barretos	Barretos	SP	Brazil	14784-400
32	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP	Brazil	01246-000
33	Instituto Brasileiro De Controle Do Câncer - IBCC; Laboratório De Patologia	São Paulo	SP	Brazil	03102-002
34	Hospital Clinico Vina del Mar	Viña del Mar		Chile	2520612
35	Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology	Hradec Kralove		Czechia	500 05
36	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc		Czechia	779 00
37	MULTISCAN, s.r.o., Radiologicke centrum Pardubice	Pardubice		Czechia	532 03
38	Oblastni nemocnice Pribram	Pribram		Czechia	261 01
39	Hospital Oncologia; Oncology	Salvador		El Salvador	01101
40	Centre Jean Perrin; Division De Recherche Clinique	Clermont Ferrand		France	63011
41	Centre Jean Bernard	Le Mans		France	72015
42	Institut Curie; Oncologie Medicale	Paris		France	75231
43	Hopital Saint Louis; Service Onco Thoracique	Paris		France	75475
44	Centre Rene Huguenin; ONCOLOGIE GENETIQUE	Saint Cloud		France	92210
45	CHI de Toulon - Hôpital Sainte Musse	Toulon		France	83056
46	Institut de Cancérologie de Lorraine	Vandoeuvre-Les-Nancy		France	54519
47	Praxisklinik Krebsheilkunde für Frauen / Brustzentrum (Dres. Kittel/Klare)	Berlin		Germany	10367
48	Studienzentrum Berlin City	Berlin		Germany	14169
49	Onkologische Schwerpunktpraxis Bielefeld	Bielefeld		Germany	33604
50	Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden	Dresden		Germany	01307
51	Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum	Essen		Germany	45136
52	Evangelische Kliniken Gelsenkirchen GmbH; Brustzentrum	Gelsenkirchen		Germany	45879
53	Universitätsklinikum Hamburg-Eppendorf (UKE); Klinik und Poliklinik für Gynäkologie	Hamburg		Germany	20246
54	Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe	Hannover		Germany	30625
55	Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Klinik für Frauenheilkunde und Geburtshilfe	Lübeck		Germany	23538
56	Rotkreuzklinikum München; Frauenklinik	Muenchen		Germany	80637
57	Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe	Münster		Germany	48149
58	Universitätsklinikum Ulm Am Michelsberg; Frauenklinik	Ulm		Germany	89075
59	Marien-Hospital Witten; Frauenklinik Brustzentrum	Witten		Germany	58452
60	Grupo Angeles	Guatemala City		Guatemala	01015
61	Centro Oncológico Sixtino / Centro Oncológico SA	Guatemala		Guatemala	01010
62	Szent Margit Hospital; Dept. of Oncology	Budapest		Hungary	1032
63	Debreceni Egyetem, Klinikai Kozpont, Onkologiai Klinika	Debrecen		Hungary	4032
64	Bacs-Kiskun Megyei Korhaz, SZTE AOK Oktato Korhaza, Onkoradiologiai Kozpont	Kecskemet		Hungary	6000
65	B-A-Z County Hospital	Miskolc		Hungary	3526
66	Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika	Szeged		Hungary	6720
67	Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica	Bologna	Emilia-Romagna	Italy	40138
68	Ospedale degli Infermi	Rimini	Emilia-Romagna	Italy	47923
69	Uni Degli Studi Di Genova ; Clinica Di Medicina Interna Ad Indirizzo Oncologico	Genova	Liguria	Italy	16132
70	ASST DI CREMONA; Dip. Medicina - S.C. Oncologia	Cremona	Lombardia	Italy	26100
71	Ospedale Per Acuti Mater Salutis Di Legnago	Legnago	Lombardia	Italy	37045
72	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1	Milano	Lombardia	Italy	20133
73	Irccs Istituto Europeo Di Oncologia (IEO); Ricerca Di Senologia Medica	Milano	Lombardia	Italy	20141
74	National Cancer Center; Medical Oncology	Gyeonggi-do		Korea, Republic of	410-769
75	Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology	Seoul		Korea, Republic of	03080
76	Yonsei University Severance Hospital; Medical Oncology	Seoul		Korea, Republic of	120-752
77	Samsung Medical Centre; Division of Hematology/Oncology	Seoul		Korea, Republic of	135-710
78	Centro Estatal de Cancerología	Chihuahua		Mexico	31000
79	Instituto Nacional De Cancerologia; Oncology; Tumores Mamarios	Distrito Federal		Mexico	14000
80	Consultorio de Medicina Especializada; Dentro de Condominio San Francisco	Mexico City		Mexico	03100
81	Centro Oncologico America	Panama		Panama	0834-02723
82	Hospital Nacional Cayetano Heredia; Hematology - Oncology	Lima		Peru	31
83	Oncosalud Sac; Oncología	Lima		Peru	41
84	Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional	Lima		Peru	Lima 41
85	Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii	Bydgoszcz		Poland	85-796
86	Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii	Gdańsk		Poland	80-952
87	Wojewódzki Szpital Specjalistyczny im. M. Kopernika; Oddział Chemioterapii	Lodz		Poland	93-513
88	Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii	Otwock		Poland	05-400
89	Wielkopolskie Centrum Onkologii; im. Marii Skłodowskiej-Curie	Poznan		Poland	61-866
90	Cent.Onkologii-Instytut im. M. S-Curie, Klinika Now. Piersi i Chirurgii Rekon	Warszawa		Poland	02-781
91	IPO de Lisboa; Servico de Oncologia Medica	Lisboa		Portugal	1099-023
92	Centro Clinico Champalimaud; Oncologia Medica	Lisboa		Portugal	1400-038
93	IPO do Porto; Servico de Oncologia Medica	Porto		Portugal	4200-072
94	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba	Spain	14004
95	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia	Santiago de Compostela	LA Coruña	Spain	15706
96	Instituto Universitario Dexeus; Servicio de Oncología	Barcelona		Spain	08028
97	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona		Spain	08035
98	Institut Catala d Oncologia Hospital Duran i Reynals	Barcelona		Spain	08908
99	Hospital San Pedro De Alcantara; Servicio de Oncologia	Caceres		Spain	10003
100	Hospital Provincial de Castellon; Servicio de Oncologia	Castellon		Spain	12002
101	Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Oncologia	Girona		Spain	17007
102	Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia	Jaen		Spain	23007
103	Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia	Lerida		Spain	25198
104	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid		Spain	28041
105	Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica	Madrid		Spain	28050
106	Hospital Universitario de Fuenlabrada; Servicio de Oncologia	Madrid		Spain	28943
107	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla		Spain	41013
108	Hospital Clinico Universitario; Oncologia	Valencia		Spain	46010
109	Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia	Valencia		Spain	46015
110	Fundación IVO	Valencia		Spain	46980
111	Kantonsspital Baden; Frauenklinik	Baden		Switzerland	5405
112	Kantonsspital Graubünden;Onkologie und Hämatologie	Chur		Switzerland	7000
113	Fondazione Oncologia Lago Maggiore	Locarno		Switzerland	6600
114	Royal Bournemouth General Hospital; Oncology	Bournemouth		United Kingdom	BH7 7DW
115	Frimley Park Hospital; Breast Resaerch Team	Camberley		United Kingdom	GU16 7UJ
116	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 0YN
117	Christie Hospital	Manchester		United Kingdom	M20 3BG

Sponsors and Collaborators

• Genentech, Inc.
• SOLTI Breast Cancer Research Group
• Breast International Group
• Austrian Breast and Colorectal Cancer Group

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Jul 27, 2015
• Statistical Analysis Plan - Jan 22, 2018

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT02273973
• Other Study ID Numbers: GO28888; 2013-000568-28
• First Posted: Oct 24, 2014
• Last Update Posted: May 21, 2018
• Last Verified: Apr 1, 2018

• Additional relevant MeSH terms: Breast Neoplasms; Letrozole

Study Results

Participant Flow

Recruitment Details	The study recruited post-menopausal participants with breast cancer in 22 countries from November 2014 to March 2017.

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Period Title: Overall Study
STARTED	166	168
COMPLETED	157	160
NOT COMPLETED	9	8

Baseline Characteristics

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole	Total
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.	Total of all reporting groups
Overall Participants	166	168	334
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.6 (8.5)	64.7 (8.7)	64.6 (8.6)
Sex: Female, Male (Count of Participants)
Female	166 100%	168 100%	334 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	143 86.1%	140 83.3%	283 84.7%
American Indian or Alaskan Native	11 6.6%	11 6.5%	22 6.6%
Asian	6 3.6%	6 3.6%	12 3.6%
Black or African American	1 0.6%	5 3%	6 1.8%
Multiple	1 0.6%	0 0%	1 0.3%
Other	3 1.8%	6 3.6%	9 2.7%
Missing	1 0.6%	0 0%	1 0.3%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	36 21.7%	48 28.6%	84 25.1%
Not Hispanic or Latino	114 68.7%	109 64.9%	223 66.8%
Not Reported	13 7.8%	10 6%	23 6.9%
Unknown	3 1.8%	1 0.6%	4 1.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Objective Response (OR) by Centrally Assessed Breast Magnetic Resonance Imaging (MRI) Via Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Version 1.1
Description	Objective response rate (ORR) was defined as proportion of participants achieving complete response (CR) or partial response (PR). As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	From Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	166	168
Number [percentage of participants]	50.0 30.1%	39.3 23.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Taselisib + Letrozole, Placebo Comparator: Placebo + Letrozole
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0490
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	10.71
	Confidence Interval	(2-Sided) 95%; 0.11 to 21.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants With Total Pathologic Complete Response (Total pCR), Defined as Having pCR in Both Breast and Axilla, Using American Joint Committee on Cancer (AJCC) Staging System
Description	Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes ( i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).
Time Frame	From Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	166	168
Number [percentage of participants]	1.8 1.1%	0.6 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Taselisib + Letrozole, Placebo Comparator: Placebo + Letrozole
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3698
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; -1.12 to 3.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in Phosphatidylinositol-4,5-Bisphosphate 3-Kinase, Catalytic Subunit Alpha (PIK3CA) Mutant (MT) Participants
Description	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	From Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	73	79
Number [percentage of participants]	56.2 33.9%	38.0 22.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Taselisib + Letrozole, Placebo Comparator: Placebo + Letrozole
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0332
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	18.19
	Confidence Interval	(2-Sided) 95%; 2.57 to 33.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Percentage of Participants With Total pCR , Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA MT Participants
Description	Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes (i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).
Time Frame	From Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	73	79
Number [percentage of participants]	1.4 0.8%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Taselisib + Letrozole, Placebo Comparator: Placebo + Letrozole
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4803
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	1.37
	Confidence Interval	(2-Sided) 95%; -1.30 to 4.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in PIK3CA Wildtype (WT) Participants
Description	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	From Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	92	89
Number [percentage of participants]	45.7 27.5%	40.4 24%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Taselisib + Letrozole, Placebo Comparator: Placebo + Letrozole
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5017
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	5.20
	Confidence Interval	(2-Sided) 95%; -9.20 to 19.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With Total pCR Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA WT Participants
Description	Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes (i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).
Time Frame	From Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	92	89
Number [percentage of participants]	2.2 1.3%	1.1 0.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Taselisib + Letrozole, Placebo Comparator: Placebo + Letrozole
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; -2.65 to 4.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA MT Participants
Description	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	From Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	73	79
Number [percentage of participants]	61.6 37.1%	40.5 24.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Taselisib + Letrozole, Placebo Comparator: Placebo + Letrozole
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0115
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	21.14
	Confidence Interval	(2-Sided) 95%; 5.59 to 36.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA WT Participants
Description	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	From Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	92	89
Number [percentage of participants]	54.3 32.7%	51.7 30.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Taselisib + Letrozole, Placebo Comparator: Placebo + Letrozole
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7928
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	2.66
	Confidence Interval	(2-Sided) 95%; -11.88 to 17.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA MT Participants
Description	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	From Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	73	79
Number [percentage of participants]	41.1 24.8%	31.6 18.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Taselisib + Letrozole, Placebo Comparator: Placebo + Letrozole
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2659
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	9.45
	Confidence Interval	(2-Sided) 95%; -5.80 to 24.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA WT Participants
Description	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	From Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	92	89
Number [percentage of participants]	40.2 24.2%	32.6 19.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Taselisib + Letrozole, Placebo Comparator: Placebo + Letrozole
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3299
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	7.63
	Confidence Interval	(2-Sided) 95%; -6.34 to 21.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA MT Participants
Description	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	From Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	73	79
Number [percentage of participants]	74.0 44.6%	63.3 37.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Taselisib + Letrozole, Placebo Comparator: Placebo + Letrozole
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1554
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	10.68
	Confidence Interval	(2-Sided) 95%; -3.96 to 25.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA WT Participants
Description	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	From Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	92	89
Number [percentage of participants]	62.0 37.3%	59.6 35.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Taselisib + Letrozole, Placebo Comparator: Placebo + Letrozole
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7870
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	2.41
	Confidence Interval	(2-Sided) 95%; -11.82 to 16.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Central Assessments of Changes in Ki67 Levels
Description	Ki67 is a prognostic marker and is used to evaluate the proliferative activity of breast cancer.
Time Frame	From Baseline to Week 3 and Surgery (Weeks 17-18); and Week 3 to Surgery (Weeks 17-18)

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	166	168
From Baseline to Week 3	-83.81	-80.44
From Baseline to Surgery	-75.58	-80.51

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Taselisib + Letrozole, Placebo Comparator: Placebo + Letrozole
	Comments	Statistical analysis for changes in Ki67 levels from Baseline to Week 3.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.117
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Ratio of Least square mean
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.65 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Experimental: Taselisib + Letrozole, Placebo Comparator: Placebo + Letrozole
	Comments	Statistical analysis for changes in Ki67 levels from Baseline to Surgery.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.105
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Ratio of Least square mean
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95%; 0.95 to 1.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Preoperative Endocrine Prognostic Index (PEPI ) Score
Description	To obtain the PEPI score, risk points for relapse-free survival (RFS) and breast cancer-specific survival (BCSS) are assigned depending on the hazard ratio (HR) from the multivariable analysis. The total PEPI score assigned to each participant is the sum of the risk points derived from the primary tumor (pT) stage, regional lymph nodes (pN) stage, Ki67 level, and estrogen receptor status of the surgical specimen. A HR in the range of 1 to 2 receives one risk point; a HR in the 2 to 2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each participant is the sum of all the risk points accumulated from the four factors in the model, ranges from 0 (best possible outcome) to 12 (worst possible outcome).
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Data were not collected for this outcome measure.

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	0	0

15. Secondary Outcome

Title	Percent Change From Baseline to Surgery in Enhancing Tumor Volume as Measured by Breast MRI
Time Frame	From Baseline to Surgery (Weeks 17-18)

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	166	168
Number (95% Confidence Interval) [percent change]	-70.60	-57.28

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Taselisib + Letrozole, Placebo Comparator: Placebo + Letrozole
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-13.32
	Confidence Interval	(2-Sided) 95%; -21.67 to -4.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Mean Score for Health-Related Quality of Life Measured by the European Organization for Research C30 (EORTC QLQ-C30)
Description	EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall quality of life (QOL) in cancer participants. The first 28 questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting [N/V], constipation, and pain) and a single item (financial difficulties). The last 2 questions represented the participant's assessment of overall health and quality of life, used 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 global scores were linearly transformed on a scale of 0 to 100, with a high score indicating better QOL. Negative change from Baseline values indicated deterioration in QOL or functioning and positive values indicated improvement. Here, Post surgery= PS.
Time Frame	Weeks 1, 5, 9, 13, 16, 4-week Post-Surgery

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	166	168
Appetite Loss: Baseline	6.2 (16.4)	5.9 (14.2)
Appetite Loss: Change at Week 5	3.0 (18.4)	1.9 (18.8)
Appetite Loss: Change at Week 9	5.3 (21.4)	3.0 (17.8)
Appetite Loss: Change at Week 13	5.5 (23.8)	2.1 (16.3)
Appetite Loss: Change at Week 16	6.8 (24.1)	0.9 (16.3)
Appetite Loss: Change at PS Visit	5.0 (24.9)	5.0 (23.3)
Cognitive functioning: Baseline	90.8 (15.8)	90.9 (16.6)
Cognitive functioning: Change at Week 5	0.4 (12.8)	-2.5 (12.3)
Cognitive functioning: Change at Week 9	-1.1 (14.4)	-4.2 (14.7)
Cognitive functioning: Change at Week 13	-3.4 (15.8)	-5.1 (15.7)
Cognitive functioning: Change at Week 16	-4.2 (15.2)	-4.1 (17.5)
Cognitive functioning: Change at PS Visit	-3.1 (18.9)	-5.4 (16.8)
Constipation: Baseline	6.8 (15.9)	8.3 (18.2)
Constipation: Change at Week 5	0.0 (16.1)	3.1 (22.1)
Constipation: Change at Week 9	0.2 (17.0)	0.2 (18.6)
Constipation: Change at Week 13	-0.4 (18.5)	-0.6 (19.5)
Constipation: Change at Week 16	-1.1 (17.2)	1.6 (20.3)
Constipation: Change at PS Visit	4.8 (23.2)	1.1 (16.9)
Diarrhoea: Baseline	5.9 (14.9)	4.3 (11.8)
Diarrhoea: Change at Week 5	6.7 (21.7)	-0.2 (13.4)
Diarrhoea: Change at Week 9	6.4 (24.3)	0.8 (15.1)
Diarrhoea: Change at Week 13	7.9 (22.3)	-0.4 (14.7)
Diarrhoea: Change at Week 16	8.4 (23.1)	0.2 (16.4)
Diarrhoea: Change at PS Visit	0.2 (17.7)	-0.9 (15.7)
Dyspnoea: Baseline	7.4 (15.8)	8.5 (17.5)
Dyspnoea: Change at Week 5	-0.2 (14.0)	0.6 (18.1)
Dyspnoea: Change at Week 9	2.0 (17.4)	1.9 (19.9)
Dyspnoea: Change at Week 13	3.5 (21.1)	1.7 (22.3)
Dyspnoea: Change at Week 16	3.4 (20.2)	2.6 (22.6)
Dyspnoea: Change at PS Visit	3.1 (24.8)	2.1 (21.5)
Emotional functioning: Baseline	77.0 (20.4)	78.2 (19.9)
Emotional functioning: Change at Week 5	4.2 (15.2)	2.4 (17.0)
Emotional functioning: Change at Week 9	3.8 (14.7)	1.3 (20.7)
Emotional functioning: Change at Week 13	2.5 (15.2)	-1.4 (18.6)
Emotional functioning: Change at Week 16	1.0 (17.0)	-3.5 (20.2)
Emotional functioning: Change at PS Visit	-0.8 (19.0)	-3.6 (20.9)
Fatigue: Baseline	14.8 (18.7)	15.6 (18.5)
Fatigue: Change at Week 5	4.7 (13.9)	4.9 (17.9)
Fatigue: Change at Week 9	5.0 (15.9)	7.5 (20.3)
Fatigue: Change at Week 13	7.9 (18.1)	8.8 (21.4)
Fatigue: Change at Week 16	6.8 (17.5)	8.0 (20.4)
Fatigue: Change at PS Visit	12.3 (19.5)	12.4 (22.6)
Financial difficulties: Baseline	9.0 (20.9)	10.0 (20.4)
Financial difficulties: Change at Week 5	-2.6 (14.6)	-0.4 (20.2)
Financial difficulties: Change at Week 9	-2.6 (17.9)	0.7 (20.4)
Financial difficulties: Change at Week 13	-1.1 (17.9)	0.0 (19.9)
Financial difficulties: Change at Week 16	-1.1 (15.9)	2.1 (24.4)
Financial difficulties: Change at PS Visit	1.9 (20.0)	3.8 (23.6)
Global health status / QoL: Baseline	75.3 (19.7)	74.6 (21.2)
Global health status / QoL: Change at Week 5	1.5 (15.2)	-1.1 (18.5)
Global health status / QoL: Change at Week 9	-1.1 (15.9)	-3.2 (22.7)
Global health status / QoL: Change at Week 13	-2.4 (19.5)	-3.7 (20.7)
Global health status / QoL: Change at Week 16	-2.2 (18.4)	-2.9 (22.6)
Global health status / QoL: Change at PS Visit	-5.9 (19.7)	-7.0 (22.2)
Insomnia: Baseline	23.0 (27.1)	22.4 (28.1)
Insomnia: Change at Week 5	-2.4 (24.1)	-0.4 (27.6)
Insomnia: Change at Week 9	-1.8 (24.9)	-0.6 (26.9)
Insomnia: Change at Week 13	-1.1 (27.7)	2.1 (29.5)
Insomnia: Change at Week 16	-0.7 (26.1)	-2.2 (27.6)
Insomnia: Change at PS Visit	-1.4 (26.8)	3.2 (34.4)
Nausea and vomiting: Baseline	1.9 (7.5)	1.6 (6.2)
Nausea and vomiting: Change at Week 5	3.7 (11.3)	1.9 (9.9)
Nausea and vomiting: Change at Week 9	3.4 (10.9)	1.7 (10.3)
Nausea and vomiting: Change at Week 13	3.7 (12.9)	0.7 (8.5)
Nausea and vomiting: Change at Week 16	2.5 (14.0)	0.6 (8.0)
Nausea and vomiting: Change at PS Visit	2.1 (14.8)	1.0 (8.6)
Pain: Baseline	13.1 (20.4)	12.3 (19.6)
Pain: Change at Week 5	-0.6 (18.8)	2.6 (17.5)
Pain: Change at Week 9	-1.8 (16.5)	3.8 (22.9)
Pain: Change at Week 13	-1.4 (18.4)	4.7 (23.4)
Pain: Change at Week 16	-0.9 (19.1)	1.8 (22.0)
Pain: Change at PS Visit	11.1 (26.0)	13.8 (26.6)
Physical functioning: Baseline	89.6 (13.7)	90.8 (13.4)
Physical functioning: Change at Week 5	0.5 (9.6)	-1.2 (11.5)
Physical functioning: Change at Week 9	0.2 (10.1)	-2.0 (13.1)
Physical functioning: Change at Week 13	-0.3 (12.4)	-1.9 (14.0)
Physical functioning: Change at Week 16	-0.5 (10.9)	-3.4 (15.1)
Physical functioning: Change at PS Visit	-5.2 (16.0)	-7.5 (15.7)
Role functioning: Baseline	90.7 (20.1)	93.1 (16.5)
Role functioning:Change at Week 5	1.3 (14.3)	-2.5 (17.1)
Role functioning:Change at Week 9	-0.2 (12.8)	-4.9 (18.9)
Role functioning:Change at Week 13	-2.3 (17.4)	-5.6 (19.8)
Role functioning:Change at Week 16	-4.6 (16.3)	-4.4 (18.9)
Role functioning:Change at PS Visit	-15.1 (24.7)	-20.1 (28.1)
Social functioning: Baseline	91.2 (17.6)	94.9 (14.3)
Social functioning: Change at Week 5	3.1 (12.8)	-2.0 (15.7)
Social functioning: Change at Week 9	2.0 (13.4)	-4.0 (18.1)
Social functioning: Change at Week 13	0.0 (13.7)	-4.0 (19.0)
Social functioning: Change at Week 16	-0.5 (13.7)	-3.1 (19.3)
Social functioning: Change at PS Visit	-6.4 (20.3)	-10.1 (24.2)

17. Secondary Outcome

Title	Mean Score for Treatment of Cancer Quality of Life Questionnaire BR23 (QLQ-BR23)
Description	EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL. Here, Post surgery= PS.
Time Frame	Weeks 1, 5, 9, 13, 16, 4-week Post-Surgery

Outcome Measure Data

Analysis Population Description

ITT population includes all randomized participants regardless of whether they received any study drug (taselisib or placebo).

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	166	168
Body image: Baseline	91.8 (15.7)	94.0 (14.6)
Body image: Change at Week 5	2.8 (8.8)	0.6 (11.4)
Body image: Change at Week 9	1.2 (9.8)	-0.2 (10.3)
Body image: Change at Week 13	1.2 (11.6)	-1.6 (13.8)
Body image: Change at Week 16	0.1 (10.8)	-1.2 (12.8)
Body image: Change at PS Visit	-6.5 (22.3)	-8.3 (19.2)
Breast symptoms: Baseline	5.3 (9.8)	6.9 (12.7)
Breast symptoms: Change at Week 5	2.3 (14.6)	1.0 (13.0)
Breast symptoms: Change at Week 9	4.5 (15.1)	1.8 (11.7)
Breast symptoms: Change at Week 13	5.8 (16.0)	2.3 (13.3)
Breast symptoms: Change at Week 16	7.9 (18.6)	3.9 (14.9)
Breast symptoms: Change at PS Visit	6.6 (17.9)	4.3 (14.2)
Future perspective: Baseline	57.7 (31.0)	58.7 (29.9)
Future perspective: Change at Week 5	6.5 (26.7)	9.3 (28.1)
Future perspective: Change at Week 9	10.2 (25.0)	9.7 (26.6)
Future perspective: Change at Week 13	7.7 (28.4)	4.4 (29.1)
Future perspective: Change at Week 16	10.2 (26.1)	5.1 (29.2)
Future perspective: Change at PS Visit	6.5 (29.7)	3.4 (34.8)
Sexual enjoyment: Baseline	41.7 (22.3)	47.1 (28.9)
Sexual enjoyment: Change at Week 5	3.3 (18.2)	11.1 (23.4)
Sexual enjoyment: Change at Week 9	8.3 (23.6)	10.6 (23.9)
Sexual enjoyment: Change at Week 13	6.1 (19.5)	1.6 (22.3)
Sexual enjoyment: Change at Week 16	9.8 (19.3)	7.6 (22.8)
Sexual enjoyment: Change at PS Visit	14.3 (27.0)	2.2 (23.5)
Sexual functioning: Baseline	81.2 (23.4)	85.1 (20.2)
Sexual functioning: Change at Week 5	1.2 (13.6)	1.0 (15.0)
Sexual functioning: Change at Week 9	1.3 (14.5)	0.3 (16.5)
Sexual functioning: Change at Week 13	4.1 (16.1)	1.6 (17.7)
Sexual functioning: Change at Week 16	4.8 (15.9)	1.1 (18.1)
Sexual functioning: Change at PS Visit	9.6 (19.2)	4.1 (21.8)
Systematic therapy side effects: Baseline	8.7 (10.8)	9.5 (11.5)
Systematic therapy side effects: Change at Week 5	4.3 (10.0)	3.9 (10.5)
Systematic therapy side effects: Change at Week 9	6.7 (10.8)	5.9 (12.1)
Systematic therapy side effects: Change at Week 13	7.3 (11.0)	6.2 (13.1)
Systematic therapy side effects: Change at Week 16	7.5 (12.9)	7.1 (12.6)
Systematic therapy side effects:Change at PS Visit	7.0 (12.0)	5.9 (12.1)
Upset by hair loss: Baseline	24.6 (26.9)	35.2 (31.3)
Upset by hair loss: Change at Week 5	11.1 (32.8)	-3.3 (18.9)
Upset by hair loss: Change at Week 9	9.1 (44.9)	-9.1 (26.2)
Upset by hair loss: Change at Week 13	16.7 (36.0)	-3.0 (34.8)
Upset by hair loss: Change at Week 16	21.2 (34.2)	-7.1 (23.3)
Upset by hair loss: Change at PS Visit	30.8 (37.2)	-2.6 (34.6)

18. Secondary Outcome

Title	Percentage of Participants With Adverse Events
Description	An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame	Baseline up to 22 weeks

Outcome Measure Data

Analysis Population Description

The safety population includes all randomized participants who received at least one dose of taselisib or placebo.

Arm/Group Title	Experimental: Taselisib + Letrozole	Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
Measure Participants	167	167
Number [percentage of participants]	91.0 54.8%	83.2 49.5%

Adverse Events

Time Frame	Baseline up to 22 weeks
Adverse Event Reporting Description	The safety population includes all randomized participants who received at least one dose of taselisib or placebo.
Arm/Group Title	Experimental: Taselisib + Letrozole		Placebo Comparator: Placebo + Letrozole
Arm/Group Description	Participants received 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.		Participants received 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
All Cause Mortality
	Experimental: Taselisib + Letrozole		Placebo Comparator: Placebo + Letrozole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/167 (0.6%)		0/167 (0%)
Serious Adverse Events
	Experimental: Taselisib + Letrozole		Placebo Comparator: Placebo + Letrozole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/167 (12%)		4/167 (2.4%)
Cardiac disorders
Cardiac failure acute	0/167 (0%)		1/167 (0.6%)
Gastrointestinal disorders
Diarrhoea	5/167 (3%)		0/167 (0%)
Colitis	2/167 (1.2%)		0/167 (0%)
Enterocolitis	1/167 (0.6%)		0/167 (0%)
Enterocolitis haemorrhagic	1/167 (0.6%)		0/167 (0%)
Stomatitis	1/167 (0.6%)		0/167 (0%)
General disorders
Impaired healing	1/167 (0.6%)		0/167 (0%)
Sudden death	1/167 (0.6%)		0/167 (0%)
Infections and infestations
Postoperative wound infection	2/167 (1.2%)		1/167 (0.6%)
Erysipelas	2/167 (1.2%)		0/167 (0%)
Bacterial diarrhoea	1/167 (0.6%)		0/167 (0%)
Cytomegalovirus infection	1/167 (0.6%)		0/167 (0%)
Diarrhoea infectious	1/167 (0.6%)		0/167 (0%)
Gastroenteritis	1/167 (0.6%)		0/167 (0%)
Haematoma infection	0/167 (0%)		1/167 (0.6%)
Pneumonia	1/167 (0.6%)		0/167 (0%)
Urinary tract infection	1/167 (0.6%)		0/167 (0%)
Metabolism and nutrition disorders
Dehydration	1/167 (0.6%)		0/167 (0%)
Nervous system disorders
Hypertensive encephalopathy	0/167 (0%)		1/167 (0.6%)
Memory impairment	1/167 (0.6%)		0/167 (0%)
Reproductive system and breast disorders
Breast pain	0/167 (0%)		1/167 (0.6%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/167 (0.6%)		0/167 (0%)
Skin and subcutaneous tissue disorders
Erythema multiforme	1/167 (0.6%)		0/167 (0%)
Rash	1/167 (0.6%)		0/167 (0%)
Other (Not Including Serious) Adverse Events
	Experimental: Taselisib + Letrozole		Placebo Comparator: Placebo + Letrozole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	130/167 (77.8%)		126/167 (75.4%)
Gastrointestinal disorders
Diarrhoea	49/167 (29.3%)		20/167 (12%)
Nausea	35/167 (21%)		19/167 (11.4%)
Stomatitis	22/167 (13.2%)		5/167 (3%)
Dry mouth	6/167 (3.6%)		14/167 (8.4%)
Constipation	10/167 (6%)		7/167 (4.2%)
Vomiting	10/167 (6%)		6/167 (3.6%)
Dyspepsia	9/167 (5.4%)		1/167 (0.6%)
General disorders
Fatigue	33/167 (19.8%)		40/167 (24%)
Asthenia	17/167 (10.2%)		16/167 (9.6%)
Infections and infestations
Viral upper respiratory tract infection	6/167 (3.6%)		13/167 (7.8%)
Urinary tract infection	7/167 (4.2%)		9/167 (5.4%)
Investigations
Alanine aminotransferase increased	9/167 (5.4%)		4/167 (2.4%)
Metabolism and nutrition disorders
Hyperglycaemia	26/167 (15.6%)		12/167 (7.2%)
Decreased appetite	11/167 (6.6%)		6/167 (3.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	19/167 (11.4%)		36/167 (21.6%)
Back pain	6/167 (3.6%)		10/167 (6%)
Nervous system disorders
Headache	16/167 (9.6%)		18/167 (10.8%)
Dizziness	9/167 (5.4%)		9/167 (5.4%)
Psychiatric disorders
Insomnia	6/167 (3.6%)		11/167 (6.6%)
Respiratory, thoracic and mediastinal disorders
Cough	9/167 (5.4%)		8/167 (4.8%)
Skin and subcutaneous tissue disorders
Alopecia	14/167 (8.4%)		8/167 (4.8%)
Rash	15/167 (9%)		5/167 (3%)
Pruritus	6/167 (3.6%)		9/167 (5.4%)
Dry skin	10/167 (6%)		3/167 (1.8%)
Vascular disorders
Hot flush	25/167 (15%)		33/167 (19.8%)
Hypertension	10/167 (6%)		11/167 (6.6%)

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.