SANDPIPER: A Study of Taselisib + Fulvestrant Versus Placebo + Fulvestrant in Participants With Advanced or Metastatic Breast Cancer Who Have Disease Recurrence or Progression During or After Aromatase Inhibitor Therapy

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02340221
• Collaborator: (none)
• Enrollment: 631
• Locations: 157
• Arms: 2
• Actual Duration (Months): 74.7
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This international, multicenter, randomized, double-blinded, placebo-controlled study is designed to compare the efficacy and safety of taselisib + fulvestrant with that of placebo + fulvestrant in postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative, oncogene that encodes for phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA)-mutant, unresectable, locally advanced or metastatic breast cancer after recurrence or progression during or after an aromatase inhibitor (AI) therapy. There will be a 2:1 randomization to the taselisib arm versus the placebo arm. Enrollment will be enriched for participants with PIK3CA mutant tumors via central testing. The anticipated duration of the study is approximately 3.5 years.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Taselisib; Drug: Placebo; Drug: Fulvestrant	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 631 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III, Double-Blind, Placebo-Controlled, Randomized Study of Taselisib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Postmenopausal Women With Estrogen Receptor-Positive and HER2-Negative Locally Advanced or Metastatic Breast Cancer Who Have Disease Recurrence or Progression During or After Aromatase Inhibitor Therapy
• Actual Study Start Date: Apr 9, 2015
• Actual Primary Completion Date: Jun 29, 2021
• Actual Study Completion Date: Jun 29, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Taselisib + Fulvestrant Participants received taselisib 4 milligrams (mg) taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Drug: Taselisib; Taselisib 4 mg was administered as two tablets of 2 mg each as per the schedule specified in the respective arm.; Other Names: GDC-0032, RO5537381 ; Drug: Fulvestrant; Fulvestrant 500 mg was administered as two IM injections of 250 mg each as per the schedule specified in the respective arms.; Other Names: Faslodex
Placebo Comparator: Placebo + Fulvestrant Participants received placebo taken orally once daily (QD) beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by intramuscular (IM) injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Drug: Placebo; Placebo matching to taselisib was administered as per the schedule specified in the respective arm.; Drug: Fulvestrant; Fulvestrant 500 mg was administered as two IM injections of 250 mg each as per the schedule specified in the respective arms.; Other Names: Faslodex

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) at Primary Analysis [From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)]

   PFS was defined as the time from randomization to disease progression as determined by the investigator with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.

2. PFS as Assessed by Investigator Using RECIST v1.1 at Final Analysis [From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)]

   PFS was defined as the time from randomization to disease progression as determined by the investigator with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.

Secondary Outcome Measures

1. Percentage of Participants With Objective Response (Partial Response [PR] Plus Complete Response [CR]), as Assessed Using RECIST v.1.1 at Primary Analysis [From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)]

   PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions).

2. Percentage of Participants With Objective Response (PR Plus CR), as Assessed Using RECIST v.1.1 at Final Analysis [From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)]

   PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions).

3. Overall Survival (OS) at Primary Analysis [From randomization up to death from any cause (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)]

   OS was defined as the time from the date of randomization to the date of death due to any cause.

4. OS at Final Analysis [From randomization up to death from any cause (up to approximately 6.2 years)]

   OS was defined as the time from the date of randomization to the date of death due to any cause.

5. Percentage of Participants With Clinical Benefit, as Assessed According to RECIST v1.1 at Primary Analysis [From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)]

   Clinical benefit was defined as objective response (PR+CR), or no disease progression lasting for more than or equal to (>/=) 24 weeks since randomization. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.

6. Percentage of Participants With Clinical Benefit, as Assessed According to RECIST v1.1 at Final Analysis [From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)]

   Clinical benefit was defined as objective response (PR+CR), or no disease progression lasting for more than or equal to (>/=) 24 weeks since randomization. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.

7. Duration of Objective Response, as Assessed by Investigator Using RECIST v1.1 at Primary Analysis [Time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)]

   Duration of objective response: the time from the first tumor assessment that supported the participant's objective response (CR or PR, whichever was first recorded) to first documented disease progression or death due to any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Disease progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.

8. Duration of Objective Response, as Assessed by Investigator Using RECIST v1.1 at Final Analysis [Time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)]

   Duration of objective response: the time from the first tumor assessment that supported the participant's objective response (CR or PR, whichever was first recorded) to first documented disease progression or death due to any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Disease progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.

9. PFS as Assessed by Blinded Independent Central Review (BICR) Using RECIST v1.1 at Primary Analysis [From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)]

   PFS was defined as the time from randomization to disease progression as determined by BICR with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.

10. PFS as Assessed by BICR Using RECIST v1.1 at Final Analysis [From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)]

    PFS was defined as the time from randomization to disease progression as determined by BICR with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.

11. Percentage of Participants With Adverse Events at Primary Analysis [From randomization up to the 15 Oct 2017 data cutoff, approximately 2.5 years.]

    An adverse event was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.

12. Percentage of Participants With Adverse Events at Final Analysis [From randomization up to approximately 6.2 years]

    An adverse event was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.

13. Maximum Observed Plasma Concentration (Cmax) of Taselisib [1 to 4 hours (hrs) post-dose on Cycle (C) 1, Day (D) 1; 0 to 3 hrs pre-dose and 2 to 6 hrs post dose on Cycle 2, Day 1 (each cycle=28 days)]

14. Minimum Observed Plasma Concentration (Cmin) of Taselisib [1 to 4 hrs post-dose on Cycle 1, Day 1; 0 to 3 hrs pre-dose and 2 to 6 hrs post dose on Cycle 2, Day 1; 0 to 3 hrs pre-dose on Cycle 6, Day 1 (each cycle=28 days)]

15. Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Score [Baseline, C2D1 up to C7D1 (each cycle=28 days)]

    The EORTC QLQ-C30 consists of 30 questions that comprise aspects of participant's functioning assessment (physical, emotional, role, cognitive, and social); symptom scales (fatigue; nausea, vomiting, and pain; the global health/quality of life [QoL]); and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties), within a recall period of "the past week." Most questions used a 4-point scale (1=Not at all to 4=Very much; two questions used a 7-point scale (1=Very poor to 7=Excellent). Scores were averaged and transformed to a 0-100 scale; a higher score for Global Qol/functional scales=better level of functioning; a higher score for symptom scale=greater degree of symptoms.

16. Change From Baseline in Modified EORTC Quality of Life Questionnaire Breast Cancer Module 23 (QLQ-BR23) Score [Baseline, C2D1 up to C7D1 (each cycle=28 days)]

    EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to a 0-100 scale. Higher scores for the functional scales indicated a higher/better level of functioning/healthy functioning. Higher scores for the symptom scales indicated worse symptoms.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Postmenopausal women with histologically or cytologically confirmed locally advanced or metastatic estrogen receptor (ER) positive breast cancer

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

• Participants for whom endocrine therapy (example [e.g.], fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study

• Radiologic/objective evidence of recurrence or progression to the most recent systemic therapy for breast cancer

• Radiologic/objective evidence of breast cancer recurrence or progression while on or within 12 months of the end of adjuvant treatment with an aromatase inhibitor (AI), or progression while on or within 1 month of the end of prior AI treatment for locally advanced or metastatic breast cancer

• Measurable disease via Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) or non-measurable, evaluable disease with at least one evaluable bone lesion via RECIST v1.1

• Consent to provide a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block (preferred) or a minimum of 20 (25 preferred) freshly cut unstained tumor slides from the most recently collected, available tumor tissue for oncogene that encodes for phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA)-mutation testing

• A valid cobas PIK3CA mutation result by central testing is required

• Adequate hematologic and end-organ function within 28 days prior to treatment initiation

Exclusion Criteria:

• Human epidermal growth factor receptor 2 (HER2)-positive disease by local laboratory testing (immunohistochemistry 3 positive [IHC 3+] staining or in situ hybridization positive)

• Prior treatment with fulvestrant

• Prior treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor, mammalian target of rapamycin (mTOR) inhibitor (e.g. everolimus), or protein kinase B (AKT) inhibitor

• Prior anti-cancer therapy within 2 weeks prior to Day 1 of Cycle 1

• Prior radiation therapy within 2 weeks prior to Day 1 of Cycle 1

• All acute treatment-related toxicity must have resolved to Grade less than or equal to (</=) 1 or be deemed stable by the Investigator

• Prior treatment with greater than (>) 1 cytotoxic chemotherapy regimen for metastatic breast cancer

• Concurrent hormone replacement therapy

• Known untreated or active central nervous system (CNS) metastases

• Type 1 or Type 2 diabetes mellitus requiring anti-hyperglycemic medications

• History of inflammatory bowel disease or active bowel inflammation

• Clinically significant cardiac or pulmonary dysfunction

• Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with human immunodeficiency virus (HIV), hepatitis B or C virus

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology	Tucson	Arizona	United States	85704
2	Arizona Oncology Associates, P.C.	Tucson	Arizona	United States	85710
3	Georgia Cancer Specialists - Northside	Atlanta	Georgia	United States	30341
4	Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital	Marietta	Georgia	United States	30060
5	Ingalls Hospital	Harvey	Illinois	United States	60426
6	Maryland Oncology Hematology	Rochville	Maryland	United States	20850
7	Dana Farber Can Ins	Boston	Massachusetts	United States	02215
8	Mercy Hospitals East Communities d/b/a Mercy Hospital St. Louis	Saint Louis	Missouri	United States	63141
9	MSKCC at Basking Ridge	Basking Ridge	New Jersey	United States	07920
10	John Theurer Cancer Ctr at Hackensack Univ Medical Ctr	Hackensack	New Jersey	United States	07601
11	Memorial Sloan-Kettering; Cancer Center	Commack	New York	United States	11725
12	Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering; at Westchester	Harrison	New York	United States	10604
13	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
14	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553
15	Oregon Health & Science University; Knight Cancer Institute, Community Hematology Oncology	Beaverton	Oregon	United States	97006
16	Pinnacle Health	Harrisburg	Pennsylvania	United States	17110
17	Liverpool Hospital; Cancer Therapy Centre	Liverpool	New South Wales	Australia	2170
18	Macquarie University Hospital	Macquarie Park	New South Wales	Australia	2109
19	Newcastle Mater Misericordiae Hospital; Oncology	Waratah	New South Wales	Australia	2298
20	Mater Hospital; Oncology	Brisbane	Queensland	Australia	4101
21	Austin Hospital; Medical Oncology	Heidelberg	Victoria	Australia	3084
22	Sunshine Hospital; Oncology Research	St Albans	Victoria	Australia
23	St John of God Murdoch Hospital; Oncology West	Murdoch	Western Australia	Australia	6150
24	Lkh-Univ. Klinikum Graz; Klinik Für Innere Medizin I	Graz		Austria	8036
25	Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie	Innsbruck		Austria	6020
26	Ordensklinikum Linz Barmherzige Schwestern; Abt. fur Innere Medizin 1	Linz		Austria	4010
27	Medizinische Universität Wien; Univ.Klinik für Innere Medizin I	Wien		Austria	1090
28	University Clinical Center of the Republic of Srpska	Banja Luka		Bosnia and Herzegovina	78000
29	Clinic of Oncology, University Clinical Center Sarajevo	Sarajevo		Bosnia and Herzegovina	7100
30	Complex Oncological Center - Plovdiv, EOOD	Plovdiv		Bulgaria	4004
31	MHAT Nadezhda	Sofia		Bulgaria	1330
32	SHATO - Sofia	Sofia		Bulgaria	1756
33	SHATOD Dr. Marko Antonov Markov-Varna, EOOD	Varna		Bulgaria	9010
34	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
35	British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
36	Grand River Hospital	Kitchener	Ontario	Canada	N2G 1G3
37	The Ottawa Hospital Cancer Centre; Oncology	Ottawa	Ontario	Canada	K1H 8L6
38	Sunnybrook Health Science Centre	Toronto	Ontario	Canada	M4N 3M5
39	McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology	Montreal	Quebec	Canada	H3T 1E2
40	Hospital Du Saint-Sacrement	Quebec City	Quebec	Canada	G1S 4L8
41	the First Hospital of Jilin University	Changchun		China	130021
42	Jilin Cancer Hospital	Changchun		China	132013
43	Jiangsu Cancer Hospital	Nanjing City		China	211100
44	Fudan University Shanghai Cancer Center	Shanghai City		China	200120
45	Zhejiang Cancer Hospital	Zhejiang		China	310022
46	Clinica del Country	Bogota		Colombia	11001
47	Oncomedica S.A.	Monteria		Colombia	230002
48	University Hospital; Oncology and Radiotherapy	Hradec Kralove		Czechia	500 05
49	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc		Czechia	779 00
50	Vseobecna fakultni nemocnice v Praze	Praha 2		Czechia	128 08
51	KYS Sadesairaala; Syopatautien poliklinikka	Kuopio		Finland	70210
52	Turku Uni Central Hospital; Oncology Clinics	Turku		Finland	20520
53	Centre Jean Perrin; Hopital De Semaine	Clermont-Ferrand		France	63011
54	Centre Georges François Leclerc; Service Pharmacie, Bp 77980	Dijon		France	21000
55	Hopital Prive Drome Ardeche; Chir 2A 2B	Guilherand Granges		France	07500
56	CHD Vendée	La Roche Sur Yon		France	85025
57	Hopital Dupuytren; Oncologie Medicale	Limoges		France	87042
58	Institut régional du Cancer Montpellier	Montpellier		France	34298
59	Institut Curie; Oncologie Medicale	Paris		France	75231
60	Ch Lyon Sud; Onco Secteur Jules Courmont	Pierre Benite		France	69495
61	Pole de Cancerologie Prive Strasbourgeois	Strasbourg		France	67000
62	Centre Alexis Vautrin; Oncologie Medicale	Vandoeuvre-les-nancy		France	54519
63	Hochwaldkrankenhaus; Abt.Gynäkologie Geburtshilfe u.Senologie	Bad Nauheim		Germany	61231
64	Praxisklinik Krebsheilkunde für Frauen / Brustzentrum (Dres. Kittel/Klare)	Berlin		Germany	10367
65	Onkologische Schwerpunktpraxis Kurfürstendamm	Berlin		Germany	10707
66	Universitätsklinikum Essen; Zentrum Für Frauenheilkunde	Essen		Germany	45122
67	Kooperatives Mammazentrum Hamburg Krankenhaus Jerusalem	Hamburg		Germany	20357
68	Klinikum der Universität München; Frauenklinik - Onkologie II	München		Germany	80337
69	Klinikum Mutterhaus der Borromäerinnen, Innere Medizin I	Trier		Germany	54290
70	Alexandras General Hospital of Athens; Oncology Department	Athens		Greece	115 28
71	IASO General Hospital of Athens	Athens		Greece	155 62
72	Univ General Hosp Heraklion; Medical Oncology	Heraklion		Greece	711 10
73	University Hospital of Patras Medical Oncology	Patras		Greece	265 04
74	Euromedical General Clinic of Thessaloniki; Oncology Department	Thessaloniki		Greece	546450
75	Papageorgiou General Hospital; Medical Oncology	Thessaloniki		Greece	564 29
76	Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica	Napoli	Campania	Italy	80131
77	ARCISPEDALE S. MARIA NUOVA - REGGIO EMILIA; Struttura Semplice Coordinamento Breast Unit Integrata	Reggio Emilia	Emilia-Romagna	Italy	42100
78	A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia	Udine	Friuli-Venezia Giulia	Italy	33100
79	IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A	Genova	Liguria	Italy	16132
80	Istituto Europeo Di Oncologia	Milano	Lombardia	Italy	20141
81	Centro Catanese Di Oncologia; Oncologia Medica	Catania	Sicilia	Italy	95126
82	Azienda Ospedaliero-Universitaria Careggi; SOD Radioterapia	Firenze	Toscana	Italy	50134
83	Azienda USL 9 Grosseto; Dipartimento Politiche del Farmaco	Grosseto	Toscana	Italy	58100
84	Azienda usl 5 Di Pisa-Ospedale Di Pontedera;U.O. Oncologia	Pontedera	Toscana	Italy	56025
85	AZ. Usll12 Veneziana-Ospedale Dell'angelo;Oncologia Medica	Mestre	Veneto	Italy	30174
86	Inje university Haeundae Paik Hospital	Busan		Korea, Republic of	48108
87	Chungbuk National University Hospital	Cheongju-si		Korea, Republic of	28644
88	National Cancer Center	Goyang-si		Korea, Republic of	10408
89	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
90	Seoul National University Hospital	Seoul		Korea, Republic of	03080
91	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
92	Asan Medical Center	Seoul		Korea, Republic of	05505
93	Samsung Medical Center	Seoul		Korea, Republic of	06351
94	Ulsan University Hosiptal	Ulsan		Korea, Republic of	44033
95	Iem-Fucam	D.f.		Mexico	04980
96	Instituto Nacional De Cancerologia; Oncology; Tumores Mamarios	Distrito Federal		Mexico	14000
97	Consultorio de Medicina Especializada; Dentro de Condominio San Francisco	Mexico City		Mexico	03100
98	Hospital San Jose Del Tec. de Monterrey; Oncology	Monterrey		Mexico	64020
99	Oaxaca Site Management Organization	Oaxaca		Mexico	68000
100	Medisch Centrum Alkmaar	Alkmaar		Netherlands	1815 JD
101	Ziekenhuis Rijnstate	Arnhem		Netherlands	6815 AD
102	Instituto Nacional de Enfermedades Neoplasicas	Lima		Peru	Lima 34
103	Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional	Lima		Peru	Lima 41
104	Oncocenter Peru S.A.C.; Oncosalud	Lima		Peru	Lima 41
105	Instituto Regional de Enfermedades Neoplasicas - IREN Norte	Trujillo		Peru	13014
106	Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej	Bialystok		Poland	15-027
107	Centrum Onkologii w Bydgoszczy; Oddzial Kliniczny Onkologii	Bydgoszcz		Poland	85-796
108	Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii	Gdansk		Poland	80-214
109	Przychodnia Lekarska KOMED, Roman Karaszewski	Konin		Poland	62-500
110	Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii	Kraków		Poland	30-688
111	Woj.Wielospecjalistyczne Centrum Onkologii i Traumatologii; Oddz.Hematologii Pododz.Chemioterapii	Lodz		Poland	93-513
112	Centrum Onkologii Ziemi LUBELSKIEJ im. Sw Jana z Dukli, I oddz. Chemioterapii	Lublin		Poland	20-090
113	Zachodniopomorskie Centrum Onkologii, Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych	Szczecin		Poland	71-730
114	Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii	Warszawa		Poland	02-781
115	Wojewodzki Szpital Specjalistyczny; Osrodek Badawczo-Rozwojowy, Oddzial Chemioterapii	Wroclaw		Poland	51-124
116	Hospital Garcia de Orta; Servico de Oncologia Medica	Almada		Portugal	2801-951
117	IPO de Lisboa; Servico de Oncologia Medica	Lisboa		Portugal	1099-023
118	Hospital da Luz; Departamento de Oncologia Medica	Lisboa		Portugal	1500-650
119	Hospital de Santa Maria; Servico de Oncologia Medica	Lisboa		Portugal	1649-035
120	IPO do Porto; Servico de Oncologia Medica	Porto		Portugal	4200-072
121	Institut of Oncology Al. Trestioreanu Bucharest; Oncology Department	Bucuresti		Romania	022328
122	Prof. Dr. I. Chiricuta Institute of Oncology	Cluj Napoca		Romania	400015
123	Oncology Center Sf. Nectarie	Craiova		Romania	200347
124	Euroclinic Center of Oncology SRL	Iasi		Romania	700106
125	Moscow City Oncology Hospital #62	Moscovskaya Oblast	Moskovskaja Oblast	Russian Federation	143423
126	Regional Clinical Oncology Dispensary; Surgery Dept, Thoracic	Arkhangelsk		Russian Federation	163045
127	Ivanovo Regional Oncology Dispensary	Ivanovo		Russian Federation	153040
128	Clinical Oncology Dispensary of Ministry of Health of Tatarstan	Kazan		Russian Federation	420029
129	State Inst. Of Healthcare Orenburg Regional Clinical Oncology Dis	Orenburg		Russian Federation	460021
130	S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)	Saint-Petersburg		Russian Federation	197758
131	Institute for Onc/Rad Serbia	Belgrade		Serbia	11000
132	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia	Santiago de Compostela	LA Coruña	Spain	15706
133	Hospital Universitario Puerta de Hierro; Servicio de Oncologia	Majadahonda	Madrid	Spain	28222
134	Hospital Universitario de Canarias;servicio de Oncologia	La Laguna	Tenerife	Spain	38320
135	Hospital de Cruces; Servicio de Oncologia	Bilbao	Vizcaya	Spain	48903
136	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
137	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona		Spain	08036
138	Centro Oncologico MD Anderson Internacional; Servicio de Oncologia	Madrid		Spain	28033
139	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid		Spain	28034
140	HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia	Madrid		Spain	28050
141	Fundación IVO	Valencia		Spain	46980
142	Hospital Universitario Miguel Servet; Servicio Oncologia	Zaragoza		Spain	50009
143	Uni Hospital Linkoeping; Dept. of Oncology	Linköping		Sweden	58185
144	Sodersjukhuset; Onkologkliniken	Stockholm		Sweden	118 83
145	Akademiska sjukhuset, Onkologkliniken	Uppsala		Sweden	751 85
146	Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology	Taipei City		Taiwan	11259
147	VETERANS GENERAL HOSPITAL; Department of General Surgery	Taipei		Taiwan	00112
148	National Taiwan Uni Hospital; General Surgery	Taipei		Taiwan	100
149	Mackay Memorial Hospital; Dept of Surgery	Taipei		Taiwan	104
150	Department of Surgery, King Chulalongkorn Memorial Hospital	Bangkok		Thailand	10330
151	Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc	Bangkok		Thailand	10400
152	Maharaj Nakorn Chiang Mai Hospital; Department of Surgery/Head Neck and Breast Unit; Clinical Trial	Chiang Mai		Thailand	50200
153	Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology	Adana		Turkey	01230
154	Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department	Edirne		Turkey	22770
155	Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology	Istanbul		Turkey	34300
156	Ege Uni Medical Faculty; Oncology Dept	Izmir		Turkey	35100
157	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye/Ankara		Turkey	06230

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 24, 2018

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02340221
• Other Study ID Numbers: GO29058; 2014-003185-25
• First Posted: Jan 16, 2015
• Last Update Posted: Jul 12, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Breast Neoplasms; Recurrence; Fulvestrant

Study Results

Participant Flow

Recruitment Details

This study was conducted at 155 centers in 28 countries.

Pre-assignment Detail

The study enrolled postmenopausal women with estrogen receptor-positive and human epidermal receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who had disease recurrence or progression during or after aromatase inhibitor therapy. Randomization was stratified by three factors: 1) visceral versus non-visceral disease, 2) sensitivity versus non-sensitivity to most recent endocrine therapy, and 3) geographical region.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Period Title: Overall Study
STARTED	214	417
COMPLETED	0	0
NOT COMPLETED	214	417

Baseline Characteristics

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant	Total
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Total of all reporting groups
Overall Participants	214	417	631
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.7 (10.0)	60.1 (9.9)	60.3 (9.9)
Sex: Female, Male (Count of Participants)
Female	214 100%	417 100%	631 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Not Hispanic or Latino	166 77.6%	334 80.1%	500 79.2%
Hispanic or Latino	26 12.1%	48 11.5%	74 11.7%
Not Stated	15 7%	15 3.6%	30 4.8%
Unknown	7 3.3%	20 4.8%	27 4.3%
Race/Ethnicity, Customized (Count of Participants)
White	147 68.7%	285 68.3%	432 68.5%
Asian	38 17.8%	72 17.3%	110 17.4%
Unknown	14 6.5%	30 7.2%	44 7%
American Indian or Alaska Native	13 6.1%	24 5.8%	37 5.9%
Black or African American	2 0.9%	2 0.5%	4 0.6%
Native Hawaiian or Other Pacific Islander	0 0%	3 0.7%	3 0.5%
Multiple	0 0%	1 0.2%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) at Primary Analysis
Description	PFS was defined as the time from randomization to disease progression as determined by the investigator with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.
Time Frame	From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)

Outcome Measure Data

Analysis Population Description

Randomized participants with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	176	340
Median (95% Confidence Interval) [months]	5.39	7.43

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Fulvestrant, Taselisib+Fulvestrant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0037
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95%; 0.56 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	PFS as Assessed by Investigator Using RECIST v1.1 at Final Analysis
Description	PFS was defined as the time from randomization to disease progression as determined by the investigator with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.
Time Frame	From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)

Outcome Measure Data

Analysis Population Description

Randomized participants with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	176	340
Median (95% Confidence Interval) [months]	5.55	8.05

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Fulvestrant, Taselisib+Fulvestrant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95%; 0.58 to 0.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Objective Response (Partial Response [PR] Plus Complete Response [CR]), as Assessed Using RECIST v.1.1 at Primary Analysis
Description	PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions).
Time Frame	From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)

Outcome Measure Data

Analysis Population Description

Randomized participants with PIK3CA-mutant tumors and measurable disease at baseline, regardless of whether they received any amount of study treatment.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	134	264
Number (95% Confidence Interval) [percentage of participants]	11.9 5.6%	28.0 6.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Fulvestrant, Taselisib+Fulvestrant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.0
	Confidence Interval	(2-Sided) 95%; 1.6 to 5.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With Objective Response (PR Plus CR), as Assessed Using RECIST v.1.1 at Final Analysis
Description	PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions).
Time Frame	From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)

Outcome Measure Data

Analysis Population Description

Randomized participants with PIK3CA-mutant tumors and measurable disease at baseline, regardless of whether they received any amount of study treatment.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	134	264
Number (95% Confidence Interval) [percentage of participants]	13.4 6.3%	31.1 7.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Fulvestrant, Taselisib+Fulvestrant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.1
	Confidence Interval	(2-Sided) 95%; 1.7 to 5.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Overall Survival (OS) at Primary Analysis
Description	OS was defined as the time from the date of randomization to the date of death due to any cause.
Time Frame	From randomization up to death from any cause (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)

Outcome Measure Data

Analysis Population Description

Randomized participants with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	176	340
Median (95% Confidence Interval) [months]	23.56	26.81

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Fulvestrant, Taselisib+Fulvestrant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4151
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.58 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	OS at Final Analysis
Description	OS was defined as the time from the date of randomization to the date of death due to any cause.
Time Frame	From randomization up to death from any cause (up to approximately 6.2 years)

Outcome Measure Data

Analysis Population Description

Randomized participants with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	176	340
Median (95% Confidence Interval) [months]	27.93	27.79

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Fulvestrant, Taselisib+Fulvestrant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9974
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants With Clinical Benefit, as Assessed According to RECIST v1.1 at Primary Analysis
Description	Clinical benefit was defined as objective response (PR+CR), or no disease progression lasting for more than or equal to (>/=) 24 weeks since randomization. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.
Time Frame	From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)

Outcome Measure Data

Analysis Population Description

Randomized participants with PIK3CA-mutant tumors and measurable disease at baseline, regardless of whether they received any amount of study treatment.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	134	264
Number (95% Confidence Interval) [percentage of participants]	37.3 17.4%	51.5 12.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Fulvestrant, Taselisib+Fulvestrant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95%; 1.2 to 2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants With Clinical Benefit, as Assessed According to RECIST v1.1 at Final Analysis
Description	Clinical benefit was defined as objective response (PR+CR), or no disease progression lasting for more than or equal to (>/=) 24 weeks since randomization. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.
Time Frame	From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)

Outcome Measure Data

Analysis Population Description

Randomized participants with PIK3CA-mutant tumors and measurable disease at baseline, regardless of whether they received any amount of study treatment.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	134	264
Number (95% Confidence Interval) [percentage of participants]	45.5 21.3%	59.5 14.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Fulvestrant, Taselisib+Fulvestrant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95%; 1.2 to 3.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Duration of Objective Response, as Assessed by Investigator Using RECIST v1.1 at Primary Analysis
Description	Duration of objective response: the time from the first tumor assessment that supported the participant's objective response (CR or PR, whichever was first recorded) to first documented disease progression or death due to any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Disease progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.
Time Frame	Time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)

Outcome Measure Data

Analysis Population Description

Randomized participants with PIK3CA-mutant tumors and measurable disease at baseline, regardless of whether they received any amount of study treatment. Data are reported for participants with responses.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	16	74
Median (95% Confidence Interval) [months]	7.23	8.74

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Fulvestrant, Taselisib+Fulvestrant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6708
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.23 to 2.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Duration of Objective Response, as Assessed by Investigator Using RECIST v1.1 at Final Analysis
Description	Duration of objective response: the time from the first tumor assessment that supported the participant's objective response (CR or PR, whichever was first recorded) to first documented disease progression or death due to any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Disease progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.
Time Frame	Time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)

Outcome Measure Data

Analysis Population Description

Randomized participants with PIK3CA-mutant tumors and measurable disease at baseline, regardless of whether they received any amount of study treatment. Data are reported for participants with responses.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	18	82
Median (95% Confidence Interval) [months]	7.39	8.97

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Fulvestrant, Taselisib+Fulvestrant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8286
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 95%; 0.51 to 2.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	PFS as Assessed by Blinded Independent Central Review (BICR) Using RECIST v1.1 at Primary Analysis
Description	PFS was defined as the time from randomization to disease progression as determined by BICR with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.
Time Frame	From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)

Outcome Measure Data

Analysis Population Description

Randomized participants with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	176	340
Median (95% Confidence Interval) [months]	5.39	8.97

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Fulvestrant, Taselisib+Fulvestrant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0023
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; 0.51 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	PFS as Assessed by BICR Using RECIST v1.1 at Final Analysis
Description	PFS was defined as the time from randomization to disease progression as determined by BICR with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression.
Time Frame	From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)

Outcome Measure Data

Analysis Population Description

Randomized participants with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	176	340
Median (95% Confidence Interval) [months]	5.55	9.20

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Fulvestrant, Taselisib+Fulvestrant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0095
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.56 to 0.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Percentage of Participants With Adverse Events at Primary Analysis
Description	An adverse event was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.
Time Frame	From randomization up to the 15 Oct 2017 data cutoff, approximately 2.5 years.

Outcome Measure Data

Analysis Population Description

The safety-evaluable population included all randomized participants who received at least one dose of taselisib or placebo or fulvestrant.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	213	416
Number [percentage of participants]	89.7 41.9%	95.4 22.9%

14. Secondary Outcome

Title	Percentage of Participants With Adverse Events at Final Analysis
Description	An adverse event was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.
Time Frame	From randomization up to approximately 6.2 years

Outcome Measure Data

Analysis Population Description

The safety-evaluable population included all randomized participants who received at least one dose of taselisib or placebo or fulvestrant.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	213	416
Number [percentage of participants]	91.1 42.6%	97.1 23.3%

15. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Taselisib
Time Frame	1 to 4 hours (hrs) post-dose on Cycle (C) 1, Day (D) 1; 0 to 3 hrs pre-dose and 2 to 6 hrs post dose on Cycle 2, Day 1 (each cycle=28 days)

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic (PK) population included all participants who received at least one dose of taselisib and provided valid (adequately documented dose time and PK sample time) PK assessments.

Arm/Group Title	Taselisib+Fulvestrant
Arm/Group Description	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	417
C1D1	18.2 (14.6)
C2D1	66.6 (35.2)

16. Secondary Outcome

Title	Minimum Observed Plasma Concentration (Cmin) of Taselisib
Time Frame	1 to 4 hrs post-dose on Cycle 1, Day 1; 0 to 3 hrs pre-dose and 2 to 6 hrs post dose on Cycle 2, Day 1; 0 to 3 hrs pre-dose on Cycle 6, Day 1 (each cycle=28 days)

Outcome Measure Data

Analysis Population Description

The PK population included all participants who received at least one dose of taselisib and provided valid (adequately documented dose time and PK sample time) PK assessments.

Arm/Group Title	Taselisib+Fulvestrant
Arm/Group Description	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	417
C2D1	42.8 (26.6)
C6D1	35.3 (31.5)

17. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Score
Description	The EORTC QLQ-C30 consists of 30 questions that comprise aspects of participant's functioning assessment (physical, emotional, role, cognitive, and social); symptom scales (fatigue; nausea, vomiting, and pain; the global health/quality of life [QoL]); and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties), within a recall period of "the past week." Most questions used a 4-point scale (1=Not at all to 4=Very much; two questions used a 7-point scale (1=Very poor to 7=Excellent). Scores were averaged and transformed to a 0-100 scale; a higher score for Global Qol/functional scales=better level of functioning; a higher score for symptom scale=greater degree of symptoms.
Time Frame	Baseline, C2D1 up to C7D1 (each cycle=28 days)

Outcome Measure Data

Analysis Population Description

Randomized participants with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment. Data are reported for evaluable participants.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	176	340
Appetite Loss: Baseline	15.9 (25.9)	15.3 (23.3)
Appetite Loss: Change at C2D1	-0.2 (25.7)	6.2 (26.2)
Appetite Loss: Change at C3D1	-4.3 (27.2)	8.7 (28.1)
Appetite Loss: Change at C4D1	-1.7 (26.1)	8.4 (28.1)
Appetite Loss: Change at C5D1	-0.4 (26.6)	6.0 (27.2)
Appetite Loss: Change at C6D1	-0.5 (22.3)	6.6 (27.2)
Appetite Loss: Change at C7D1	-5.7 (28.7)	4.6 (26.5)
Cognitive Functioning: Baseline	85.3 (18.1)	85.9 (18.7)
Cognitive Functioning: Change at C2D1	0.7 (16.5)	-1.1 (16.8)
Cognitive Functioning: Change at C3D1	0.9 (17.9)	-2.9 (19.1)
Cognitive Functioning: Change at C4D1	1.8 (18.9)	-1.7 (18.4)
Cognitive Functioning: Change at C5D1	-1.5 (17.7)	-3.2 (17.7)
Cognitive Functioning: Change at C6D1	-0.5 (18.5)	-2.8 (17.6)
Cognitive Functioning: Change at C7D1	-2.3 (18.1)	-0.8 (18.8)
Constipation: Baseline	15.8 (23.9)	14.5 (23.7)
Constipation: Change at C2D1	0.0 (24.0)	-6.0 (21.1)
Constipation: Change at C3D1	-2.3 (25.0)	-4.9 (20.8)
Constipation: Change at C4D1	-2.7 (24.6)	-5.5 (22.0)
Constipation: Change at C5D1	-1.3 (22.7)	-4.0 (21.0)
Constipation: Change at C6D1	-3.0 (27.3)	-3.5 (21.8)
Constipation: Change at C7D1	-4.6 (24.5)	-6.9 (22.5)
Diarrhoea: Baseline	6.3 (15.1)	5.0 (14.4)
Diarrhoea: Change at C2D1	-0.5 (17.9)	10.2 (22.4)
Diarrhoea: Change at C3D1	-0.9 (16.6)	13.7 (26.3)
Diarrhoea: Change at C4D1	-2.7 (21.0)	13.1 (28.9)
Diarrhoea: Change at C5D1	-2.6 (19.4)	11.1 (27.7)
Diarrhoea: Change at C6D1	-2.0 (17.4)	14.0 (29.1)
Diarrhoea: Change at C7D1	1.1 (20.7)	15.6 (30.9)
Dyspnoea: Baseline	15.0 (23.0)	15.4 (22.2)
Dyspnoea: Change at C2D1	4.1 (23.5)	-2.1 (19.5)
Dyspnoea: Change at C3D1	2.8 (20.3)	0.0 (20.9)
Dyspnoea: Change at C4D1	0.7 (23.2)	0.0 (23.3)
Dyspnoea: Change at C5D1	2.6 (26.5)	1.6 (23.2)
Dyspnoea: Change at C6D1	3.0 (26.6)	0.2 (23.4)
Dyspnoea: Change at C7D1	1.7 (24.5)	-2.1 (21.2)
Emotional Functioning: Baseline	73.1 (22.1)	71.9 (22.1)
Emotional Functioning: Change at C2D1	4.0 (17.9)	5.1 (18.5)
Emotional Functioning: Change at C3D1	4.5 (19.1)	2.3 (21.6)
Emotional Functioning: Change at C4D1	4.5 (18.5)	2.6 (19.7)
Emotional Functioning: Change at C5D1	5.2 (20.1)	-0.4 (21.8)
Emotional Functioning: Change at C6D1	2.1 (20.5)	2.4 (21.6)
Emotional Functioning: Change at C7D1	5.3 (20.7)	2.8 (19.7)
Fatigue: Baseline	30.8 (22.5)	30.8 (22.0)
Fatigue: Change at C2D1	2.0 (19.2)	-0.5 (18.8)
Fatigue: Change at C3D1	-1.5 (19.5)	1.8 (21.5)
Fatigue: Change at C4D1	-0.2 (19.1)	2.4 (21.9)
Fatigue: Change at C5D1	-0.1 (20.8)	2.8 (20.4)
Fatigue: Change at C6D1	3.3 (20.0)	2.4 (20.5)
Fatigue: Change at C7D1	1.0 (20.0)	1.8 (20.5)
Financial Difficulties: Baseline	18.5 (25.8)	19.2 (27.1)
Financial Difficulties: Change at C2D1	-1.1 (20.4)	-2.8 (21.4)
Financial Difficulties: Change at C3D1	-0.9 (24.9)	-1.6 (24.4)
Financial Difficulties: Change at C4D1	0.7 (25.1)	-0.3 (23.7)
Financial Difficulties: Change at C5D1	-0.4 (28.0)	0.3 (24.9)
Financial Difficulties: Change at C6D1	5.6 (30.1)	0.4 (23.6)
Financial Difficulties: Change at C7D1	-0.6 (26.1)	2.1 (23.1)
Global Health Status/ QoL: Baseline	65.2 (18.4)	67.4 (20.3)
Global Health Status/ QoL: Change at C2D1	-0.1 (16.7)	1.0 (19.9)
Global Health Status/ QoL: Change at C3D1	-1.0 (18.5)	-1.5 (20.9)
Global Health Status/ QoL: Change at C4D1	-1.5 (18.6)	-1.6 (20.3)
Global Health Status/ QoL: Change at C5D1	0.3 (19.9)	-2.8 (20.3)
Global Health Status/ QoL: Change at C6D1	-1.6 (18.6)	-3.4 (19.5)
Global Health Status/ QoL: Change at C7D1	-1.1 (18.9)	-1.0 (18.9)
Insomnia: Baseline	26.0 (27.6)	26.5 (27.7)
Insomnia: Change at C2D1	-0.9 (24.4)	-3.8 (23.7)
Insomnia: Change at C3D1	-3.4 (30.1)	-4.1 (26.4)
Insomnia: Change at C4D1	-4.0 (28.9)	-1.0 (26.8)
Insomnia: Change at C5D1	-0.4 (29.1)	-3.9 (25.6)
Insomnia: Change at C6D1	-2.0 (30.3)	-2.4 (28.2)
Insomnia: Change at C7D1	-4.1 (28.2)	-1.8 (27.2)
Nausea/Vomiting: Baseline	5.9 (13.4)	6.7 (13.7)
Nausea/Vomiting: Change at C2D1	0.1 (11.9)	1.6 (18.1)
Nausea/Vomiting: Change at C3D1	0.7 (15.2)	2.2 (17.6)
Nausea/Vomiting: Change at C4D1	0.3 (17.9)	2.3 (18.6)
Nausea/Vomiting: Change at C5D1	-1.1 (18.3)	0.5 (15.4)
Nausea/Vomiting: Change at C6D1	1.5 (18.0)	-0.6 (15.9)
Nausea/Vomiting: Change at C7D1	2.6 (15.5)	2.2 (18.8)
Pain: Baseline	28.0 (25.4)	27.1 (24.9)
Pain: Change at C2D1	-0.2 (24.0)	-5.0 (20.8)
Pain: Change at C3D1	-3.7 (23.3)	-3.5 (22.6)
Pain: Change at C4D1	-3.2 (24.7)	-1.7 (24.2)
Pain: Change at C5D1	-3.3 (24.2)	-4.3 (22.9)
Pain: Change at C6D1	-1.0 (23.0)	-2.2 (22.5)
Pain: Change at C7D1	0.3 (23.5)	-4.4 (19.8)
Physical Functioning: Baseline	76.7 (19.9)	78.4 (18.8)
Physical Functioning: Change at C2D1	-1.1 (13.4)	1.6 (12.7)
Physical Functioning: Change at C3D1	2.0 (14.1)	0.8 (15.7)
Physical Functioning: Change at C4D1	1.5 (16.1)	0.3 (15.7)
Physical Functioning: Change at C5D1	2.0 (17.7)	1.0 (13.5)
Physical Functioning: Change at C6D1	0.9 (18.4)	1.1 (14.9)
Physical Functioning: Change at C7D1	1.6 (16.2)	0.6 (14.2)
Role Functioning: Baseline	79.1 (24.6)	78.7 (24.0)
Role Functioning: Change at C2D1	-2.0 (19.3)	1.7 (21.5)
Role Functioning: Change at C3D1	-0.4 (23.4)	-1.0 (23.9)
Role Functioning: Change at C4D1	0.3 (23.0)	0.4 (24.2)
Role Functioning: Change at C5D1	1.8 (22.5)	-1.6 (21.6)
Role Functioning: Change at C6D1	-1.3 (23.8)	-1.6 (23.4)
Role Functioning: Change at C7D1	-0.3 (22.6)	0.0 (22.9)
Social Functioning: Baseline	83.2 (21.8)	81.2 (23.1)
Social Functioning: Change at C2D1	-0.8 (19.9)	2.7 (20.0)
Social Functioning: Change at C3D1	1.3 (21.9)	-0.8 (23.2)
Social Functioning: Change at C4D1	1.8 (18.2)	-0.5 (21.3)
Social Functioning: Change at C5D1	0.9 (19.4)	-1.0 (23.3)
Social Functioning: Change at C6D1	-0.8 (20.1)	-1.6 (23.4)
Social Functioning: Change at C7D1	0.6 (21.2)	0.1 (19.7)

18. Secondary Outcome

Title	Change From Baseline in Modified EORTC Quality of Life Questionnaire Breast Cancer Module 23 (QLQ-BR23) Score
Description	EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to a 0-100 scale. Higher scores for the functional scales indicated a higher/better level of functioning/healthy functioning. Higher scores for the symptom scales indicated worse symptoms.
Time Frame	Baseline, C2D1 up to C7D1 (each cycle=28 days)

Outcome Measure Data

Analysis Population Description

Randomized participants with PIK3CA-mutant tumors, regardless of whether they received any amount of study treatment. Data are reported for evaluable participants.

Arm/Group Title	Placebo+Fulvestrant	Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.	Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
Measure Participants	176	340
Arm Symptoms: Baseline	15.5 (18.8)	19.3 (21.1)
Arm Symptoms: Change at C2D1	0.1 (17.4)	-5.4 (15.6)
Arm Symptoms: Change at C3D1	-0.7 (19.5)	-6.1 (17.4)
Arm Symptoms: Change at C4D1	-1.4 (21.9)	-5.8 (15.8)
Arm Symptoms: Change at C5D1	0.8 (17.0)	-6.6 (15.7)
Arm Symptoms: Change at C6D1	1.1 (20.8)	-5.0 (18.5)
Arm Symptoms: Change at C7D1	-1.2 (19.7)	-6.0 (15.2)
Body Image: Baseline	82.0 (21.7)	80.8 (22.5)
Body Image: Change at C2D1	1.8 (14.9)	1.5 (16.5)
Body Image: Change at C3D1	1.6 (18.0)	1.1 (20.6)
Body Image: Change at C4D1	1.1 (17.8)	1.8 (20.6)
Body Image: Change at C5D1	0.2 (19.5)	0.0 (17.5)
Body Image: Change at C6D1	1.1 (21.0)	0.4 (18.2)
Body Image: Change at C7D1	5.6 (18.8)	-0.3 (18.2)
Breast Symptoms: Baseline	8.7 (14.6)	11.0 (14.1)
Breast Symptoms: Change at C2D1	0.0 (13.7)	-3.0 (11.8)
Breast Symptoms: Change at C3D1	-0.8 (13.3)	-3.5 (11.6)
Breast Symptoms: Change at C4D1	0.1 (14.2)	-3.0 (11.8)
Breast Symptoms: Change at C5D1	-0.9 (14.5)	-2.0 (11.7)
Breast Symptoms: Change at C6D1	1.7 (16.0)	-2.0 (12.9)
Breast Symptoms: Change at C7D1	0.3 (12.6)	-3.2 (13.1)
Future Perspective: Baseline	47.4 (31.5)	47.3 (29.6)
Future Perspective: Change at C2D1	3.4 (30.1)	6.8 (27.4)
Future Perspective: Change at C3D1	5.1 (29.5)	4.3 (30.5)
Future Perspective: Change at C4D1	6.0 (30.7)	7.0 (29.2)
Future Perspective: Change at C5D1	6.0 (30.3)	5.0 (26.8)
Future Perspective: Change at C6D1	6.9 (28.8)	9.0 (31.4)
Future Perspective: Change at C7D1	12.9 (29.4)	7.0 (30.2)
Sexual Enjoyment: Baseline	51.9 (26.7)	62.8 (26.6)
Sexual Enjoyment: Change at C2D1	5.9 (21.2)	0.0 (18.1)
Sexual Enjoyment: Change at C3D1	4.8 (22.1)	1.3 (24.0)
Sexual Enjoyment: Change at C4D1	-8.3 (15.4)	4.2 (24.7)
Sexual Enjoyment: Change at C5D1	-4.8 (23.0)	2.6 (29.7)
Sexual Enjoyment: Change at C6D1	-6.7 (14.9)	-5.9 (24.3)
Sexual Enjoyment: Change at C7D1	-13.3 (29.8)	9.5 (20.4)
Sexual Functioning: Baseline	89.6 (17.9)	89.9 (17.3)
Sexual Functioning: Change at C2D1	1.6 (11.0)	1.5 (14.2)
Sexual Functioning: Change at C3D1	1.4 (10.6)	1.8 (15.6)
Sexual Functioning: Change at C4D1	1.9 (15.4)	1.6 (13.9)
Sexual Functioning: Change at C5D1	-0.8 (20.6)	2.6 (15.1)
Sexual Functioning: Change at C6D1	2.4 (18.8)	2.7 (15.0)
Sexual Functioning: Change at C7D1	2.7 (18.1)	2.3 (15.7)
Systematic Therapy SEs: Baseline	15.7 (14.2)	14.7 (12.0)
Systematic Therapy SEs: Change at C2D1	0.2 (11.4)	2.5 (11.0)
Systematic Therapy SEs: Change at C3D1	1.2 (14.4)	4.0 (13.6)
Systematic Therapy SEs: Change at C4D1	1.5 (13.2)	4.0 (13.3)
Systematic Therapy SEs: Change at C5D1	2.4 (13.8)	5.5 (14.1)
Systematic Therapy SEs: Change at C6D1	2.9 (15.2)	5.7 (15.6)
Systematic Therapy SEs: Change at C7D1	3.5 (16.7)	4.8 (15.0)
Upset by Hair Loss: Baseline	23.2 (28.2)	27.0 (29.2)
Upset by Hair Loss: Change at C2D1	-11.9 (28.1)	-4.3 (22.3)
Upset by Hair Loss: Change at C3D1	-7.7 (30.9)	0.0 (26.7)
Upset by Hair Loss: Change at C4D1	2.6 (16.5)	0.0 (29.2)
Upset by Hair Loss: Change at C5D1	0.0 (25.2)	10.7 (27.3)
Upset by Hair Loss: Change at C6D1	11.1 (27.2)	16.7 (30.2)
Upset by Hair Loss: Change at C7D1	4.2 (11.8)	14.1 (32.9)

Adverse Events

Time Frame	From randomization up to the end of study, approximately 6.2 years
Adverse Event Reporting Description	All-cause mortality was reported based on the ITT population: all randomized participants regardless of whether they received any amount of study treatment. Serious and non-serious adverse events were reported based on the safety-evaluable population: all randomized participants who received at least one dose of taselisib, placebo or fulvestrant regardless of the PIK3CA-mutation status of their tumors with participants allocated to the treatment arm associated with the regimen actually received.
Arm/Group Title	Placebo+Fulvestrant		Taselisib+Fulvestrant
Arm/Group Description	Participants received placebo taken orally QD beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.		Participants received taselisib 4 mg taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.
All Cause Mortality
	Placebo+Fulvestrant		Taselisib+Fulvestrant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	100/214 (46.7%)		197/417 (47.2%)
Serious Adverse Events
	Placebo+Fulvestrant		Taselisib+Fulvestrant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/213 (10.8%)		154/416 (37%)
Blood and lymphatic system disorders
ANAEMIA	1/213 (0.5%)	2	2/416 (0.5%)	2
PANCYTOPENIA	0/213 (0%)	0	1/416 (0.2%)	1
Cardiac disorders
ATRIAL FIBRILLATION	0/213 (0%)	0	2/416 (0.5%)	2
CARDIAC FAILURE CONGESTIVE	0/213 (0%)	0	1/416 (0.2%)	1
MYOCARDIAL INFARCTION	0/213 (0%)	0	1/416 (0.2%)	1
SUPRAVENTRICULAR TACHYCARDIA	0/213 (0%)	0	1/416 (0.2%)	1
Gastrointestinal disorders
ABDOMINAL PAIN	0/213 (0%)	0	1/416 (0.2%)	1
ABDOMINAL PAIN UPPER	0/213 (0%)	0	1/416 (0.2%)	1
ALCOHOLIC PANCREATITIS	0/213 (0%)	0	1/416 (0.2%)	1
COLITIS	0/213 (0%)	0	16/416 (3.8%)	17
DIARRHOEA	0/213 (0%)	0	37/416 (8.9%)	40
DYSPEPSIA	0/213 (0%)	0	1/416 (0.2%)	1
DYSPHAGIA	0/213 (0%)	0	1/416 (0.2%)	1
ENTERITIS	0/213 (0%)	0	1/416 (0.2%)	1
ENTEROCOLITIS	0/213 (0%)	0	3/416 (0.7%)	3
GASTRIC ULCER	0/213 (0%)	0	1/416 (0.2%)	1
GASTRITIS	0/213 (0%)	0	2/416 (0.5%)	2
NAUSEA	2/213 (0.9%)	2	4/416 (1%)	5
OESOPHAGEAL ULCER	0/213 (0%)	0	1/416 (0.2%)	1
OESOPHAGITIS	0/213 (0%)	0	1/416 (0.2%)	1
PANCREATITIS	0/213 (0%)	0	1/416 (0.2%)	1
PANCREATITIS ACUTE	0/213 (0%)	0	2/416 (0.5%)	2
SMALL INTESTINAL OBSTRUCTION	0/213 (0%)	0	2/416 (0.5%)	3
STOMATITIS	0/213 (0%)	0	2/416 (0.5%)	2
VOMITING	1/213 (0.5%)	1	4/416 (1%)	4
General disorders
ASTHENIA	0/213 (0%)	0	1/416 (0.2%)	1
CHEST DISCOMFORT	0/213 (0%)	0	2/416 (0.5%)	2
CHEST PAIN	0/213 (0%)	0	3/416 (0.7%)	3
CHILLS	1/213 (0.5%)	1	0/416 (0%)	0
DEATH	1/213 (0.5%)	1	3/416 (0.7%)	3
FATIGUE	1/213 (0.5%)	1	2/416 (0.5%)	2
MUCOSAL INFLAMMATION	0/213 (0%)	0	1/416 (0.2%)	1
PAIN	1/213 (0.5%)	1	0/416 (0%)	0
PYREXIA	2/213 (0.9%)	2	3/416 (0.7%)	3
SWELLING FACE	1/213 (0.5%)	1	0/416 (0%)	0
Hepatobiliary disorders
CHOLECYSTITIS ACUTE	0/213 (0%)	0	1/416 (0.2%)	1
CHOLELITHIASIS	0/213 (0%)	0	1/416 (0.2%)	1
HEPATOTOXICITY	0/213 (0%)	0	1/416 (0.2%)	1
Immune system disorders
ANAPHYLACTIC SHOCK	0/213 (0%)	0	1/416 (0.2%)	1
Infections and infestations
APPENDICITIS PERFORATED	0/213 (0%)	0	1/416 (0.2%)	1
ATYPICAL MYCOBACTERIAL PNEUMONIA	0/213 (0%)	0	1/416 (0.2%)	1
BRONCHITIS	0/213 (0%)	0	1/416 (0.2%)	1
CELLULITIS	0/213 (0%)	0	2/416 (0.5%)	2
CHOLERA	0/213 (0%)	0	1/416 (0.2%)	1
CLOSTRIDIUM DIFFICILE COLITIS	0/213 (0%)	0	1/416 (0.2%)	1
CYSTITIS ESCHERICHIA	0/213 (0%)	0	1/416 (0.2%)	1
DIARRHOEA INFECTIOUS	0/213 (0%)	0	3/416 (0.7%)	3
ENTEROCOLITIS INFECTIOUS	0/213 (0%)	0	2/416 (0.5%)	2
GASTROENTERITIS	0/213 (0%)	0	1/416 (0.2%)	1
GASTROENTERITIS VIRAL	0/213 (0%)	0	1/416 (0.2%)	1
HERPES ZOSTER	0/213 (0%)	0	1/416 (0.2%)	1
LOWER RESPIRATORY TRACT INFECTION	0/213 (0%)	0	1/416 (0.2%)	1
PNEUMONIA	1/213 (0.5%)	1	10/416 (2.4%)	10
RESPIRATORY TRACT INFECTION	0/213 (0%)	0	1/416 (0.2%)	1
SEPSIS	1/213 (0.5%)	1	5/416 (1.2%)	5
SEPTIC ARTHRITIS STAPHYLOCOCCAL	0/213 (0%)	0	1/416 (0.2%)	2
SKIN INFECTION	0/213 (0%)	0	2/416 (0.5%)	2
URINARY TRACT INFECTION	0/213 (0%)	0	3/416 (0.7%)	3
UROSEPSIS	0/213 (0%)	0	1/416 (0.2%)	1
VIRAL INFECTION	0/213 (0%)	0	1/416 (0.2%)	1
Injury, poisoning and procedural complications
CLAVICLE FRACTURE	0/213 (0%)	0	1/416 (0.2%)	1
FALL	1/213 (0.5%)	1	2/416 (0.5%)	2
FEMORAL NECK FRACTURE	1/213 (0.5%)	1	0/416 (0%)	0
FEMUR FRACTURE	0/213 (0%)	0	1/416 (0.2%)	1
HIP FRACTURE	1/213 (0.5%)	1	0/416 (0%)	0
JOINT DISLOCATION	0/213 (0%)	0	1/416 (0.2%)	1
TOXICITY TO VARIOUS AGENTS	0/213 (0%)	0	1/416 (0.2%)	1
WRIST FRACTURE	1/213 (0.5%)	1	0/416 (0%)	0
Investigations
ALANINE AMINOTRANSFERASE INCREASED	1/213 (0.5%)	1	2/416 (0.5%)	2
ASPARTATE AMINOTRANSFERASE INCREASED	1/213 (0.5%)	1	1/416 (0.2%)	1
WHITE BLOOD CELL COUNT DECREASED	1/213 (0.5%)	1	0/416 (0%)	0
Metabolism and nutrition disorders
DECREASED APPETITE	0/213 (0%)	0	1/416 (0.2%)	1
DEHYDRATION	1/213 (0.5%)	1	7/416 (1.7%)	7
HYPERGLYCAEMIA	0/213 (0%)	0	7/416 (1.7%)	7
Musculoskeletal and connective tissue disorders
ARTHRALGIA	0/213 (0%)	0	2/416 (0.5%)	3
BACK PAIN	0/213 (0%)	0	1/416 (0.2%)	1
COCCYDYNIA	0/213 (0%)	0	1/416 (0.2%)	1
MUSCLE SPASMS	1/213 (0.5%)	2	0/416 (0%)	0
MUSCULAR WEAKNESS	1/213 (0.5%)	1	0/416 (0%)	0
OSTEONECROSIS OF JAW	1/213 (0.5%)	1	0/416 (0%)	0
RHABDOMYOLYSIS	0/213 (0%)	0	1/416 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
HEPATOCELLULAR CARCINOMA	0/213 (0%)	0	1/416 (0.2%)	1
INTRACRANIAL TUMOUR HAEMORRHAGE	0/213 (0%)	0	1/416 (0.2%)	1
Nervous system disorders
CEREBRAL HAEMATOMA	0/213 (0%)	0	1/416 (0.2%)	1
CEREBROVASCULAR ACCIDENT	2/213 (0.9%)	2	1/416 (0.2%)	1
FACIAL PARALYSIS	1/213 (0.5%)	1	0/416 (0%)	0
HEADACHE	0/213 (0%)	0	3/416 (0.7%)	3
HYPOAESTHESIA	0/213 (0%)	0	2/416 (0.5%)	2
TRANSIENT ISCHAEMIC ATTACK	0/213 (0%)	0	1/416 (0.2%)	1
TRIGEMINAL NEURALGIA	0/213 (0%)	0	1/416 (0.2%)	1
VITH NERVE PARALYSIS	1/213 (0.5%)	1	0/416 (0%)	0
Psychiatric disorders
CONFUSIONAL STATE	0/213 (0%)	0	1/416 (0.2%)	1
MENTAL STATUS CHANGES	0/213 (0%)	0	2/416 (0.5%)	2
Renal and urinary disorders
ACUTE KIDNEY INJURY	0/213 (0%)	0	4/416 (1%)	4
HAEMATURIA	0/213 (0%)	0	1/416 (0.2%)	1
RENAL FAILURE	0/213 (0%)	0	1/416 (0.2%)	1
URETEROLITHIASIS	1/213 (0.5%)	1	0/416 (0%)	0
Reproductive system and breast disorders
INTERMENSTRUAL BLEEDING	0/213 (0%)	0	1/416 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME	0/213 (0%)	0	1/416 (0.2%)	1
ACUTE RESPIRATORY FAILURE	0/213 (0%)	0	1/416 (0.2%)	1
COUGH	0/213 (0%)	0	1/416 (0.2%)	1
DYSPNOEA	1/213 (0.5%)	1	1/416 (0.2%)	1
INTERSTITIAL LUNG DISEASE	0/213 (0%)	0	1/416 (0.2%)	1
PLEURAL EFFUSION	2/213 (0.9%)	2	1/416 (0.2%)	2
PLEURITIC PAIN	1/213 (0.5%)	1	0/416 (0%)	0
PNEUMONITIS	1/213 (0.5%)	1	10/416 (2.4%)	10
PNEUMOTHORAX	0/213 (0%)	0	2/416 (0.5%)	2
PULMONARY EMBOLISM	0/213 (0%)	0	1/416 (0.2%)	1
PULMONARY OEDEMA	1/213 (0.5%)	1	0/416 (0%)	0
RESPIRATORY FAILURE	0/213 (0%)	0	1/416 (0.2%)	1
Skin and subcutaneous tissue disorders
DRUG ERUPTION	0/213 (0%)	0	1/416 (0.2%)	1
PRURITUS	0/213 (0%)	0	1/416 (0.2%)	1
RASH	0/213 (0%)	0	2/416 (0.5%)	2
RASH MACULO-PAPULAR	0/213 (0%)	0	1/416 (0.2%)	1
TOXIC SKIN ERUPTION	0/213 (0%)	0	1/416 (0.2%)	1
Vascular disorders
EMBOLISM	0/213 (0%)	0	1/416 (0.2%)	1
EMBOLISM VENOUS	0/213 (0%)	0	1/416 (0.2%)	1
HYPERTENSION	0/213 (0%)	0	1/416 (0.2%)	1
SHOCK	0/213 (0%)	0	1/416 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Placebo+Fulvestrant		Taselisib+Fulvestrant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	183/213 (85.9%)		396/416 (95.2%)
Blood and lymphatic system disorders
ANAEMIA	20/213 (9.4%)	23	44/416 (10.6%)	62
NEUTROPENIA	9/213 (4.2%)	12	28/416 (6.7%)	39
Gastrointestinal disorders
ABDOMINAL PAIN	20/213 (9.4%)	25	55/416 (13.2%)	67
ABDOMINAL PAIN UPPER	8/213 (3.8%)	8	31/416 (7.5%)	35
CONSTIPATION	32/213 (15%)	36	32/416 (7.7%)	36
DIARRHOEA	45/213 (21.1%)	76	255/416 (61.3%)	602
DRY MOUTH	18/213 (8.5%)	19	55/416 (13.2%)	62
DYSPEPSIA	5/213 (2.3%)	5	32/416 (7.7%)	51
GASTROOESOPHAGEAL REFLUX DISEASE	4/213 (1.9%)	4	23/416 (5.5%)	25
NAUSEA	54/213 (25.4%)	71	154/416 (37%)	233
STOMATITIS	8/213 (3.8%)	11	87/416 (20.9%)	139
VOMITING	25/213 (11.7%)	41	86/416 (20.7%)	116
General disorders
ASTHENIA	40/213 (18.8%)	65	77/416 (18.5%)	104
FATIGUE	40/213 (18.8%)	51	105/416 (25.2%)	134
MUCOSAL INFLAMMATION	11/213 (5.2%)	15	44/416 (10.6%)	67
OEDEMA PERIPHERAL	11/213 (5.2%)	13	19/416 (4.6%)	25
PYREXIA	9/213 (4.2%)	10	48/416 (11.5%)	61
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION	11/213 (5.2%)	17	33/416 (7.9%)	41
URINARY TRACT INFECTION	9/213 (4.2%)	10	38/416 (9.1%)	50
Investigations
ALANINE AMINOTRANSFERASE INCREASED	9/213 (4.2%)	13	36/416 (8.7%)	47
ASPARTATE AMINOTRANSFERASE INCREASED	15/213 (7%)	19	35/416 (8.4%)	47
BLOOD ALKALINE PHOSPHATASE INCREASED	12/213 (5.6%)	12	15/416 (3.6%)	17
BLOOD CREATININE INCREASED	6/213 (2.8%)	7	25/416 (6%)	28
WEIGHT DECREASED	6/213 (2.8%)	6	42/416 (10.1%)	50
Metabolism and nutrition disorders
DECREASED APPETITE	23/213 (10.8%)	25	119/416 (28.6%)	136
HYPERGLYCAEMIA	21/213 (9.9%)	26	166/416 (39.9%)	233
HYPOKALAEMIA	2/213 (0.9%)	2	31/416 (7.5%)	37
Musculoskeletal and connective tissue disorders
ARTHRALGIA	35/213 (16.4%)	50	69/416 (16.6%)	95
BACK PAIN	28/213 (13.1%)	32	62/416 (14.9%)	82
BONE PAIN	17/213 (8%)	19	24/416 (5.8%)	26
MUSCLE SPASMS	6/213 (2.8%)	8	32/416 (7.7%)	34
MYALGIA	14/213 (6.6%)	14	36/416 (8.7%)	42
PAIN IN EXTREMITY	19/213 (8.9%)	27	33/416 (7.9%)	42
Nervous system disorders
DIZZINESS	18/213 (8.5%)	23	46/416 (11.1%)	58
DYSGEUSIA	5/213 (2.3%)	5	36/416 (8.7%)	41
HEADACHE	27/213 (12.7%)	38	88/416 (21.2%)	122
Psychiatric disorders
INSOMNIA	18/213 (8.5%)	19	37/416 (8.9%)	40
Respiratory, thoracic and mediastinal disorders
COUGH	34/213 (16%)	41	64/416 (15.4%)	78
DYSPNOEA	17/213 (8%)	17	50/416 (12%)	53
Skin and subcutaneous tissue disorders
ALOPECIA	6/213 (2.8%)	6	50/416 (12%)	53
DRY SKIN	10/213 (4.7%)	10	37/416 (8.9%)	40
PRURITUS	18/213 (8.5%)	28	52/416 (12.5%)	75
RASH	17/213 (8%)	24	80/416 (19.2%)	116
Vascular disorders
HOT FLUSH	27/213 (12.7%)	27	24/416 (5.8%)	26
HYPERTENSION	11/213 (5.2%)	16	33/416 (7.9%)	42

Limitations/Caveats

[Not Specified]

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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.