BELLE-2: Phase III Study of BKM120/Placebo With Fulvestrant in Postmenopausal Patients With Hormone Receptor Positive HER2-negative Locally Advanced or Metastatic Breast Cancer Refractory to Aromatase Inhibitor

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01610284
• Collaborator: (none)
• Enrollment: 1,147
• Locations: 268
• Arms: 2
• Actual Duration (Months): 80.4
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study was a multi-center, randomized, double-blind, placebo controlled Phase III study to determine the efficacy and safety of treatment with buparlisib plus fulvestrant versus fulvestrant plus placebo in postmenopausal women with hormone Receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative), locally advanced or metastatic breast cancer (MBC) whose disease has progressed on or after aromatase inhibitor (AI) treatment.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Fulvestrant; Drug: BKM120; Drug: BKM120 matching placebo	Phase 3

Detailed Description

Patients were randomized (1:1) to receive buparlisib (100 mg/day) or placebo with fulvestrant (500 mg); randomization was stratified by PI3K pathway activation status (activated, non-activated, unknown determined in archival tumor tissue) and visceral disease status (present or absent). Tumor evaluation was performed 6 weeks after the randomization date and then every 8 weeks until radiological progression (based on Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1).

Novartis made the decision not to pursue further development of buparlisib and to terminate the ongoing studies in the program. Accordingly, on 19-Dec-2016, Novartis notified all the Investigators about the decision not to pursue further development of buparlisib in Breast Cancer. As a result, the CBKM120F2302 study was terminated on 19-Apr-2019 (last subject last visit).

Study Design

• Study Type: Interventional
• Actual Enrollment: 1147 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized, Double Blind Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative Locally Advanced or Metastatic Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment
• Actual Study Start Date: Aug 7, 2012
• Actual Primary Completion Date: Apr 29, 2015
• Actual Study Completion Date: Apr 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BKM120 100mg + Fulvestrant BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Drug: Fulvestrant; Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter); Drug: BKM120; BKM120 100 mg once daily
Placebo Comparator: Placebo + Fulvestrant BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.	Drug: Fulvestrant; Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter); Drug: BKM120 matching placebo; BKM120 matching placebo, once daily

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort [Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to approximately 4 years]

   Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm.

Secondary Outcome Measures

1. Overall Survival (OS) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort [Every 3 months following end of treatment visit, assessed for approximately 5 years]

   Overall Survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up for the duration of the study and for an expected average of every 3 months after end of treatment.

2. Overall Response Rate (ORR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort [From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years]

   Overall Response Rate (ORR) is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1. ORR was analyzed in the full population. Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target/non target lesions: Complete Response (CR), disappearance of all target/non target lesions (all lymph nodes assigned as non-target lesions must be non-pathological in size (< 10 mm short axis)); Partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions ; Overall Response (OR)= CR+PR. Only descriptive analysis performed.

3. Clinical Benefit Rate (CBR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort [From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years]

   Clinical Benefit Rate (CBR) is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or Non-CR/non-PD lasting more than 24 weeks based on local investigator's assessment according to RECIST 1.1. CBR was analyzed in the full population. Only descriptive analysis performed.

4. Number of Participants With On-Treatments Adverse Events, Serious Adverse Events and Deaths [From first dose of study treatment to 30 days after last dose of study treatment, assessed for approximately 5 years]

   Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths. Only descriptive analysis performed.

5. Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 2 Day 1 [Cycle2 Day1 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours post-dose). Each cycle is 28 days.]

   Plasma samples were collected from the first 200 BKM120-treated patients on Cycle 2 Day 1 (at pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h and 24h [before Cycle 2 Day 2 dose] post-dose). Each cycle is 28 days. Only descriptive analysis performed.

6. Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS) [Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1. Each cycle is 28 days.]

   Pre-dose samples were collected for trough concentrations at Cycle 2 Day 1, Cycle 2 Day 15 and Cycle 3 Day 1. Each cycle is 28 days. Only descriptive analysis performed.

7. Median Time to Definitive Deterioration of the ECOG Performance Status - Full Analysis Set (FAS) [Up to approx 27 months]

   Time to definitive deterioration of the ECOG PS was defined as the time between the date of randomization and the date of the assessment at which definitive deterioration was seen. Only descriptive analysis performed.

8. Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 [Cycle 1 day 1, cycle 1 day 15, 6 weeks after randomisation and then every 8 weeks until end of treatment]

   The global health status/QoL scale score of the QLQ-C30 is identified as the primary PRO variable of interest. Physical Functioning (PF), Emotional Functioning (EF) and Social Functioning (SF) scale scores of the QLQ-C30. The time to definitive 10% deterioration is defined as the time from the randomization date to the date of an event, which is defined as a worsening (decrease) in score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study or death due to any cause. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high /healthy level of functioning, a high score for the global health status / QoL represents a high QoL. Patients were assessed up to approx. 8.3 months. Only descriptive analysis performed.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Locally advanced or metastatic breast cancer

• HER2-negative and hormone receptor-positive status (common breast cancer classification tests)

• Postmenopausal woman

• A tumor sample must be shipped to a Novartis designated laboratory for identification of biomarkers (PI3K activation status)

• Progression or recurrence of breast cancer while on or after aromatase inhibitor treatment

• Measurable disease or non measurable disease bone lesions in the absence of measurable disease as per RECIST 1.1

• Adequate bone marrow and organ function defined by laboratory values

Key Exclusion Criteria:

• Previous treatment with PI3K inhibitors, AKT inhibitors, mTOR inhibitor or fulvestrant

• More than one prior chemotherapy line for metastatic disease

• Symptomatic brain metastases

• Increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent

• Active heart (cardiac) disease as defined in the protocol

• Certain scores on an anxiety and depression mood questionnaires

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of South Alabama / Mitchell Cancer Institute Deptof Mitchell Cancer Inst(2)	Mobile	Alabama	United States	36688
2	Arizona Oncology Associates Dept of Oncology	Phoenix	Arizona	United States
3	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
4	Shapiro and Stafford and Yee and Polanski Study Coordinator	Arcadia	California	United States	91007
5	Cancer Care Associates Dept.ofCancerCareAssoc.	Fresno	California	United States	93720
6	St. Jude Heritage Medical Group Virginia Crosson Cancer Center	Fullerton	California	United States	92835
7	University of California San Diego - Moores Cancer Center UCSD 3	La Jolla	California	United States	92093-0658
8	Los Angeles Hematology/Oncology Medical Group LA Cancer Network	Los Angeles	California	United States	90017
9	USC Kenneth Norris Comprehensive Cancer Center Dept.ofNorrisCompCancerCtr (3)	Los Angeles	California	United States	90053
10	University of California at Los Angeles Dept. of UCLA	Los Angeles	California	United States	90095
11	Ventura County Hematology and Oncology PMK Medical Group	Oxnard	California	United States	93030
12	Coastal Integrative Cancer Care	San Luis Obispo	California	United States	93401
13	Santa Barbara Hematolgy Oncology Medical Group	Santa Barbara	California	United States	93105
14	Central Coast Medical Oncology Corporation	Santa Maria	California	United States	93454
15	St Joseph Heritage Healthcare Dept. of RRMG (4)	Santa Rosa	California	United States	94503
16	Granada Hills Cancer Center	Valencia	California	United States	91355
17	Kaiser Permanente Northwest Kaiser	Denver	Colorado	United States
18	Rocky Mountain Cancer Centers RMCC	Greenwood Village	Colorado	United States
19	Memorial Regional Cancer Center MRCC	Hollywood	Florida	United States	33021
20	Cancer Specialists of North Florida SC - F2302	Jacksonville	Florida	United States	32258
21	University of Miami Univ Miami 2	Miami	Florida	United States	33136
22	MD Anderson Cancer Center - Orlando MD Orlando	Orlando	Florida	United States	32806
23	Georgia Cancer Specialists SC	Decatur	Georgia	United States	30033
24	North Shore University Health System	Evanston	Illinois	United States	60201
25	Cadence Health	Geneva	Illinois	United States	60134
26	Cancer Care and Hematology Specialists of Chicagoland Niles	Multiple Locations	Illinois	United States
27	Cancer Center of Kansas CCK	Wichita	Kansas	United States	67214-3728
28	Mercy Medical Center Mercy Medical SC	Baltimore	Maryland	United States	21202
29	Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Med Sidney/John Hopkins	Baltimore	Maryland	United States	21231
30	Frederick Memorial Hospital Fred. Mem. Hosp.	Frederick	Maryland	United States	21701
31	Maryland Oncology Hematology, P.A. SC	Rockville	Maryland	United States	20850
32	Massachusetts General Hospital SC	Boston	Massachusetts	United States	02114
33	West Michigan Cancer Center Dept of Oncology	Kalamazoo	Michigan	United States	49007
34	Hematology and Oncology Association at Bridgepoint Hem Onc Bridgepoint	Tupelo	Mississippi	United States	38801
35	Washington University School of Medicine Regulatory	Saint Louis	Missouri	United States	63110
36	Hackensack Meridian Health	Brick	New Jersey	United States	08724
37	The Valley Hospital / Luckow Pavillion	Paramus	New Jersey	United States	07652
38	Clinical Research Alliance SC-2	Lake Success	New York	United States	11042
39	Memorial Sloan Kettering Dept Onc	New York	New York	United States	10017
40	University of Rochester Medical Center Univ Rochester	Rochester	New York	United States	14642
41	Levine Cancer Institute Levine Cancer Institute	Charlotte	North Carolina	United States	28203
42	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
43	Case Western Reserve SC	Cleveland	Ohio	United States	44106-5000
44	Northwest Cancer Specialists Portland Loc	Portland	Oregon	United States	97210
45	St. Luke's Hospital and Health Network St Luke's (2)	Bethlehem	Pennsylvania	United States	18015
46	Charleston Hematology Oncology Association PA	Charleston	South Carolina	United States	29414
47	Tennessee Cancer Specialists	Knoxville	Tennessee	United States	37909
48	Vanderbilt University Medical Center Vanderbilt - Thompson Ln	Nashville	Tennessee	United States	37232
49	Texas Oncology P A Midtown	Dallas	Texas	United States	75251
50	Texas Oncology P A TX Onc - Bedford	Dallas	Texas	United States	75251
51	Texas Oncology P A TX Onc - Med City Dallas	Dallas	Texas	United States	75251
52	Texas Oncology P A TX Onc - Southwest	Dallas	Texas	United States	75251
53	Oncology Consultants Oncology Consultants, P.A.	Houston	Texas	United States	77024
54	Cancer Therapy and Research Center UT Health Science Center Institute for Drug Development	San Antonio	Texas	United States	78229
55	Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)	Salt Lake City	Utah	United States	84106
56	Oncology Hematology Associates of Southeast Virginia Salem VA Branch	Roanoke	Virginia	United States	24014
57	Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc	Kennewick	Washington	United States	99336
58	West Virginia University/ Mary Babb Randolph Cancer Center Dept of Oncology	Morgantown	West Virginia	United States	26506
59	Cancer TEAM Bellin Health Belin Health	Green Bay	Wisconsin	United States	54313
60	Dean Health System Dean Hematology Oncology	Madison	Wisconsin	United States	53717
61	University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 3	Madison	Wisconsin	United States	53792-6164
62	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1050AAK
63	Novartis Investigative Site	Mar del Plata	Buenos Aires	Argentina	B7600CTO
64	Novartis Investigative Site	San Miguel De Tucuman	Tucuman	Argentina	T4000IAK
65	Novartis Investigative Site	Rio Negro	Viedma	Argentina	8500
66	Novartis Investigative Site	Sydney	New South Wales	Australia	2060
67	Novartis Investigative Site	Woollongong	New South Wales	Australia	2500
68	Novartis Investigative Site	South Brisbane	Queensland	Australia	4101
69	Novartis Investigative Site	Clayton	Victoria	Australia	3168
70	Novartis Investigative Site	Melbourne	Victoria	Australia	3000
71	Novartis Investigative Site	Murdoch	Western Australia	Australia	6150
72	Novartis Investigative Site	Nedlands	Western Australia	Australia	6009
73	Novartis Investigative Site	Linz		Austria	4010
74	Novartis Investigative Site	Salzburg		Austria	5020
75	Novartis Investigative Site	Wien		Austria	A-1090
76	Novartis Investigative Site	Jette	Brussel	Belgium	1090
77	Novartis Investigative Site	Bruxelles		Belgium	1000
78	Novartis Investigative Site	Charleroi		Belgium	6000
79	Novartis Investigative Site	Leuven		Belgium	3000
80	Novartis Investigative Site	Liege		Belgium	4000
81	Novartis Investigative Site	Namur		Belgium	5000
82	Novartis Investigative Site	Wilrijk		Belgium	2610
83	Novartis Investigative Site	Belo Horizonte	MG	Brazil	30150-270
84	Novartis Investigative Site	Curitiba	PR	Brazil	81520-060
85	Novartis Investigative Site	Natal	RN	Brazil	59075 740
86	Novartis Investigative Site	Ijuí	RS	Brazil	98700-000
87	Novartis Investigative Site	Barretos	SP	Brazil	14784 400
88	Novartis Investigative Site	Sao Paulo	SP	Brazil	01246 000
89	Novartis Investigative Site	Sorocaba	SP	Brazil
90	Novartis Investigative Site	Calgary	Alberta	Canada	T2N 4N2
91	Novartis Investigative Site	Edmonton	Alberta	Canada	T6G 1Z2
92	Novartis Investigative Site	Kelowna	British Columbia	Canada	V1Y 5L3
93	Novartis Investigative Site	Vancouver	British Columbia	Canada	V5Z 4E6
94	Novartis Investigative Site	Halifax	Nova Scotia	Canada	B3H 1V7
95	Novartis Investigative Site	Cambridge	Ontario	Canada	N1R 3G2
96	Novartis Investigative Site	London	Ontario	Canada	N6A 4L6
97	Novartis Investigative Site	Newmarket	Ontario	Canada	J7Y 2P9
98	Novartis Investigative Site	Ottawa	Ontario	Canada	K1H 8L6
99	Novartis Investigative Site	Toronto	Ontario	Canada	M4N 3M5
100	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 2M9
101	Novartis Investigative Site	Laval	Quebec	Canada	H7M 3L9
102	Novartis Investigative Site	Montreal	Quebec	Canada	H2L 4M1
103	Novartis Investigative Site	Regina	Saskatchewan	Canada	S4T 7T1
104	Novartis Investigative Site	Quebec		Canada	G1S 4L8
105	Novartis Investigative Site	Harbin	Heilongjiang	China	150081
106	Novartis Investigative Site	Changsha	Hunan	China	410013
107	Novartis Investigative Site	Nanjing	Jiangsu	China	210009
108	Novartis Investigative Site	Shengyang	Liaoning	China	110042
109	Novartis Investigative Site	Shanghai	Shanghai	China	200032
110	Novartis Investigative Site	Chengdu	Sichuan	China	610041
111	Novartis Investigative Site	Hangzhou	Zhejiang	China	310022
112	Novartis Investigative Site	Beijing		China	100039
113	Novartis Investigative Site	Guangzhou		China	510060
114	Novartis Investigative Site	Shanghai		China	200025
115	Novartis Investigative Site	Brno Bohunice	Czech Republic	Czechia	625 00
116	Novartis Investigative Site	Olomouc	CZE	Czechia	775 20
117	Novartis Investigative Site	Brno		Czechia	65653
118	Novartis Investigative Site	Nice Cedex 2	Alpes Maritimes	France	06189
119	Novartis Investigative Site	Dijon Cedex	Cote D Or	France	21034
120	Novartis Investigative Site	Saint Priest en Jarez	Loire	France	42270
121	Novartis Investigative Site	Angers Cedex 02		France	49055
122	Novartis Investigative Site	Avignon Cedex		France	84082
123	Novartis Investigative Site	Besancon cedex		France	25030
124	Novartis Investigative Site	Bordeaux		France	33076
125	Novartis Investigative Site	Caen Cedex		France	14021
126	Novartis Investigative Site	Clermont-Ferrand		France	63011
127	Novartis Investigative Site	Le Mans Cedex		France	72015
128	Novartis Investigative Site	Lille Cedex		France	59020
129	Novartis Investigative Site	Montpellier Cedex 5		France	34298
130	Novartis Investigative Site	Paris		France	75010
131	Novartis Investigative Site	Paris		France	75231
132	Novartis Investigative Site	Rouen Cedex 1		France	76038
133	Novartis Investigative Site	Saint-Herblain Cédex		France	44805
134	Novartis Investigative Site	Strasbourg cedex		France	67085
135	Novartis Investigative Site	Toulouse Cedex 9		France	31059
136	Novartis Investigative Site	Villejuif Cedex		France	94800
137	Novartis Investigative Site	Langen	Hessen	Germany	63225
138	Novartis Investigative Site	Recklinghausen	North Rhine-westphalia	Germany	45657
139	Novartis Investigative Site	Luebeck	Schleswig-holstein	Germany	23563
140	Novartis Investigative Site	Essen		Germany	45147
141	Novartis Investigative Site	Hamburg		Germany	20249
142	Novartis Investigative Site	Hannover		Germany	30177
143	Novartis Investigative Site	Heidelberg		Germany	69120
144	Novartis Investigative Site	Kiel		Germany	24105
145	Novartis Investigative Site	Magdeburg		Germany	39108
146	Novartis Investigative Site	Mainz		Germany	55131
147	Novartis Investigative Site	Mannheim		Germany	68165
148	Novartis Investigative Site	Mühlhausen		Germany	99974
149	Novartis Investigative Site	München		Germany	80638
150	Novartis Investigative Site	Saarbruecken		Germany	66113
151	Novartis Investigative Site	Velbert		Germany	42551
152	Novartis Investigative Site	Wuerzburg		Germany	97080
153	Novartis Investigative Site	Thessaloniki	GR	Greece	54645
154	Novartis Investigative Site	Athens		Greece	115 28
155	Novartis Investigative Site	Heraklion Crete		Greece	711 10
156	Novartis Investigative Site	Patras		Greece	265 00
157	Novartis Investigative Site	Budapest		Hungary	H 1122
158	Novartis Investigative Site	Debrecen		Hungary	4032
159	Novartis Investigative Site	Miskolc		Hungary	3526
160	Novartis Investigative Site	Szolnok		Hungary	H-5000
161	Novartis Investigative Site	Haifa		Israel	3525408
162	Novartis Investigative Site	Jerusalem		Israel	91120
163	Novartis Investigative Site	Petach Tikva		Israel	49100
164	Novartis Investigative Site	Ramat Gan		Israel	52621
165	Novartis Investigative Site	Tel Aviv		Israel	6423906
166	Novartis Investigative Site	Cuneo	CN	Italy	12100
167	Novartis Investigative Site	Cremona	CR	Italy	26100
168	Novartis Investigative Site	Catanzaro	CZ	Italy	88100
169	Novartis Investigative Site	Meldola	FC	Italy	47014
170	Novartis Investigative Site	Firenze	FI	Italy	50134
171	Novartis Investigative Site	Lido di Camaiore	LU	Italy	55041
172	Novartis Investigative Site	Macerata	MC	Italy	62100
173	Novartis Investigative Site	Milano	MI	Italy	20122
174	Novartis Investigative Site	Milano	MI	Italy	20133
175	Novartis Investigative Site	Milano	MI	Italy	20141
176	Novartis Investigative Site	Milano	MI	Italy	20162
177	Novartis Investigative Site	Rozzano	MI	Italy	20089
178	Novartis Investigative Site	Pisa	PI	Italy	56126
179	Novartis Investigative Site	Aviano	PN	Italy	33081
180	Novartis Investigative Site	Roma	RM	Italy	00128
181	Novartis Investigative Site	Roma	RM	Italy	00161
182	Novartis Investigative Site	Roma	RM	Italy	00189
183	Novartis Investigative Site	Rimini	RN	Italy	47900
184	Novartis Investigative Site	Torino	TO	Italy	10126
185	Novartis Investigative Site	Mirano	VE	Italy	30035
186	Novartis Investigative Site	Bologna		Italy	40138
187	Novartis Investigative Site	Napoli		Italy	80131
188	Novartis Investigative Site	Nagoya	Aichi	Japan	464 8681
189	Novartis Investigative Site	Kashiwa	Chiba	Japan	277 8577
190	Novartis Investigative Site	Fukuoka-city	Fukuoka	Japan	811-1395
191	Novartis Investigative Site	Maebashi city	Gunma	Japan	371 8511
192	Novartis Investigative Site	Sapporo-city	Hokkaido	Japan	003-0804
193	Novartis Investigative Site	Isehara	Kanagawa	Japan	259-1193
194	Novartis Investigative Site	Yokohama-city	Kanagawa	Japan	241-8515
195	Novartis Investigative Site	Kumamoto City	Kumamoto	Japan	860-8556
196	Novartis Investigative Site	Sakyo Ku	Kyoto	Japan	606 8507
197	Novartis Investigative Site	Osaka-city	Osaka	Japan	540-0006
198	Novartis Investigative Site	Osaka-city	Osaka	Japan	541-8567
199	Novartis Investigative Site	Suita city	Osaka	Japan	565 0871
200	Novartis Investigative Site	Koto ku	Tokyo	Japan	135 8550
201	Novartis Investigative Site	Suwon	Gyeonggi-do	Korea, Republic of	443380
202	Novartis Investigative Site	Seoul	Seocho Gu	Korea, Republic of	06591
203	Novartis Investigative Site	Seoul		Korea, Republic of	03080
204	Novartis Investigative Site	Seoul		Korea, Republic of	03722
205	Novartis Investigative Site	Seoul		Korea, Republic of	06351
206	Novartis Investigative Site	Nijmegen		Netherlands	6500 HB
207	Novartis Investigative Site	Surquillo	Lima	Peru	34
208	Novartis Investigative Site	Kraków		Poland
209	Novartis Investigative Site	Olsztyn		Poland	10-513
210	Novartis Investigative Site	Warszawa		Poland	02-776
211	Novartis Investigative Site	Moscow		Russian Federation	115478
212	Novartis Investigative Site	Moscow		Russian Federation	115998
213	Novartis Investigative Site	Nizhniy Novgorod		Russian Federation	603081
214	Novartis Investigative Site	St Petersburg		Russian Federation	197758
215	Novartis Investigative Site	St- Petersburg		Russian Federation	197022
216	Novartis Investigative Site	Singapore		Singapore	169610
217	Novartis Investigative Site	Bratislava	Slovak Republic	Slovakia	83310
218	Novartis Investigative Site	Kosice		Slovakia	041 91
219	Novartis Investigative Site	Johannesburg		South Africa	2196
220	Novartis Investigative Site	Parktown		South Africa	2193
221	Novartis Investigative Site	Elche	Alicante	Spain	03203
222	Novartis Investigative Site	Cordoba	Andalucia	Spain	14004
223	Novartis Investigative Site	Jaen	Andalucia	Spain	23007
224	Novartis Investigative Site	Malaga	Andalucia	Spain	29010
225	Novartis Investigative Site	Sevilla	Andalucia	Spain	41009
226	Novartis Investigative Site	Sevilla	Andalucia	Spain	41013
227	Novartis Investigative Site	Sevilla	Andalucia	Spain	41014
228	Novartis Investigative Site	Oviedo	Asturias	Spain	33006
229	Novartis Investigative Site	Toledo	Castilla La Mancha	Spain	45071
230	Novartis Investigative Site	Barcelona	Catalunya	Spain	08003
231	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
232	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
233	Novartis Investigative Site	Barcelona	Cataluña	Spain	08024
234	Novartis Investigative Site	Tarragona	Cataluña	Spain	43007
235	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46009
236	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46010
237	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46026
238	Novartis Investigative Site	Las Palmas De Gran Canarias	Las Palmas De Gran Canaria	Spain	35016
239	Novartis Investigative Site	San Sebastian de los Reyes	Madrid	Spain	28702
240	Novartis Investigative Site	El Palmar	Murcia	Spain	30120
241	Novartis Investigative Site	Barcelona		Spain	08041
242	Novartis Investigative Site	Madrid		Spain	28009
243	Novartis Investigative Site	Madrid		Spain	28033
244	Novartis Investigative Site	Madrid		Spain	28040
245	Novartis Investigative Site	Madrid		Spain	28046
246	Novartis Investigative Site	Madrid		Spain	28050
247	Novartis Investigative Site	Madrid		Spain	28222
248	Novartis Investigative Site	Zaragoza		Spain	50009
249	Novartis Investigative Site	Bellinzona		Switzerland	6500
250	Novartis Investigative Site	Genève		Switzerland	1211
251	Novartis Investigative Site	Zuerich		Switzerland	8038
252	Novartis Investigative Site	Kaohsiung		Taiwan	80756
253	Novartis Investigative Site	Kaohsiung		Taiwan	833
254	Novartis Investigative Site	Taichung		Taiwan	40447
255	Novartis Investigative Site	Taipei		Taiwan	10048
256	Novartis Investigative Site	Taipei		Taiwan	112
257	Novartis Investigative Site	Bangkok		Thailand	10330
258	Novartis Investigative Site	Bangkok		Thailand	10400
259	Novartis Investigative Site	Bangkok		Thailand	10700
260	Novartis Investigative Site	Truro	Cornwall	United Kingdom	TR1 3LJ
261	Novartis Investigative Site	Bournemouth		United Kingdom	BH7 7DW
262	Novartis Investigative Site	Derby		United Kingdom	DE22 3NE
263	Novartis Investigative Site	Leicester		United Kingdom	LE1 5WW
264	Novartis Investigative Site	Liverpool		United Kingdom	L7 8XP
265	Novartis Investigative Site	London		United Kingdom	SE1 9RT
266	Novartis Investigative Site	London		United Kingdom	WC1E 6HX
267	Novartis Investigative Site	Manchester		United Kingdom	M20 2BX
268	Novartis Investigative Site	Oxford		United Kingdom	OX3 7LJ

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01610284
• Other Study ID Numbers: CBKM120F2302; 2011-005524-17
• First Posted: Jun 4, 2012
• Last Update Posted: Aug 25, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Breast cancer; Hormone receptor positive; HER2-negative; Metastatic; Locally advanced; PI3K; Fulvestrant; Refractory; Aromatase inhibitor
• Additional relevant MeSH terms: Breast Neoplasms; Fulvestrant

Study Results

Participant Flow

Recruitment Details	This study was conducted at 274 centers in 29 countries worldwide (Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czech Republic, France, Germany, Greece, Hungary, Israel, Italy, Japan, Republic of Korea, The Netherlands, Peru, Poland, Russia, Singapore, Slovakia, South Africa, Spain, Switzerland, Taiwan, Thailand, UK and USA.).
Pre-assignment Detail	Approximately 1200 patients were planned to be enrolled in the study. A total of 1147 patients were randomized and analyzed (576 in the buparlisib + fulvestrant and 571 in the placebo + fulvestrant arm). Not completed: in Randomization Phase=Randomized and not Treated; in Treatment Phase=Discontinued study treatment per Protocol.

Arm/Group Title	BKM120 100mg + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Period Title: Randomization Phase
STARTED	576	571
Safety Set (SS)	573	570
COMPLETED	574	569
NOT COMPLETED	2	2
Period Title: Randomization Phase
STARTED	574	569
BKM120 Pharmacokinetic Analysis Set	93	0
Full Pharmacokinetic Analysis Set (FPAS)	35	0
COMPLETED	0	0
NOT COMPLETED	574	569
Period Title: Randomization Phase
STARTED	89	29
COMPLETED	0	0
NOT COMPLETED	89	29

Baseline Characteristics

Arm/Group Title	BKM120 100mg + Fulvestrant	Placebo + Fulvestrant	Total
Arm/Group Description	BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.	Total of all reporting groups
Overall Participants	576	571	1147
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	329 57.1%	378 66.2%	707 61.6%
>=65 years	247 42.9%	193 33.8%	440 38.4%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.2 (10.20)	60.6 (10.08)	61.4 (10.17)
Sex: Female, Male (Count of Participants)
Female	576 100%	571 100%	1147 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
Asian	132 22.9%	153 26.8%	285 24.8%
Black	5 0.9%	16 2.8%	21 1.8%
Caucasian	402 69.8%	376 65.8%	778 67.8%
Other	18 3.1%	7 1.2%	25 2.2%
Unknown	19 3.3%	18 3.2%	37 3.2%
Missing	0 0%	1 0.2%	1 0.1%
ECOG Performance Status (Count of Participants)
Grade 0 = No Restrictions	333 57.8%	344 60.2%	677 59%
Grade 1 = Only Light Work	231 40.1%	211 37%	442 38.5%
Grade 2 = Only Self Care	11 1.9%	16 2.8%	27 2.4%
Grade 3 = Only Limited Self-Care	1 0.2%	0 0%	1 0.1%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort
Description	Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm.
Time Frame	Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to approximately 4 years

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) in the Full Population, the Main Study Cohort (known PI3K pathway activation status [activated, non activated]) and the PI3K unknown cohort (PI3K pathway unknown status) were considered.

Arm/Group Title	BKM120 100mg + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Measure Participants	576	571
FAS-Full population	6.9	5.0
FAS-Main cohort	6.8	4.5
FAS-PI3K pathway activated	6.8	4.0
FAS-PI3K pathway non-activated	6.9	4.6
FAS-PI3K pathway unknown	8.7	6.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BKM120 100mg + Fulvestrant, Placebo + Fulvestrant
	Comments	FAS-Full population
	Type of Statistical Test	Other
	Comments	Comparison of progression-free survival (PFS) (based on local investigator assessment) between the two treatment groups using a stratified log-rank test at one-sided 2.5% level of significance
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.67 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BKM120 100mg + Fulvestrant, Placebo + Fulvestrant
	Comments	FAS-Main cohort
	Type of Statistical Test	Other
	Comments	Comparison of progression-free survival (PFS) (based on local investigator assessment) between the two treatment groups using a stratified log-rank test at one-sided 2.5% level of significance
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; 0.68 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	BKM120 100mg + Fulvestrant, Placebo + Fulvestrant
	Comments	FAS-PI3K pathway activated
	Type of Statistical Test	Other
	Comments	Comparison of progression-free survival (PFS) (based on local investigator assessment) between the two treatment groups using a stratified log-rank test at one-sided 2.5% level of significance
Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95%; 0.60 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BKM120 100mg + Fulvestrant, Placebo + Fulvestrant
	Comments	FAS-PI3K pathway non-activated
	Type of Statistical Test	Other
	Comments	Comparison of progression-free survival (PFS) (based on local investigator assessment) between the two treatment groups using a stratified log-rank test at one-sided 2.5% level of significance
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.67 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BKM120 100mg + Fulvestrant, Placebo + Fulvestrant
	Comments	FAS-PI3K pathway unknown
	Type of Statistical Test	Other
	Comments	Comparison of progression-free survival (PFS) (based on local investigator assessment) between the two treatment groups using a stratified log-rank test at one-sided 2.5% level of significance
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95%; 0.52 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Survival (OS) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort
Description	Overall Survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up for the duration of the study and for an expected average of every 3 months after end of treatment.
Time Frame	Every 3 months following end of treatment visit, assessed for approximately 5 years

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) in the Full Population, the Main Study Cohort (known PI3K pathway activation status [activated, non activated]) and the PI3K unknown cohort (PI3K pathway unknown status) were considered.

Arm/Group Title	BKM120 100mg + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Measure Participants	576	571
FAS-Full population	33.2	30.4
FAS-Main cohort	30.9	28.9
FAS-PI3K pathway activated	33.6	27.5
FAS-PI3K pathway non-activated	28.8	30.0
FAS-PI3K pathway unknown	42.3	36.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BKM120 100mg + Fulvestrant, Placebo + Fulvestrant
	Comments	FAS-Full population
	Type of Statistical Test	Other
	Comments	Comparison of overall survival (OS) (based on local investigator assessment) between the two treatment groups using a stratified log-rank test at one-sided 2.5% level of significance
Statistical Test of Hypothesis	p-Value	0.045
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.74 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BKM120 100mg + Fulvestrant, Placebo + Fulvestrant
	Comments	FAS-Main cohort
	Type of Statistical Test	Other
	Comments	Comparison of overall survival (OS) (based on local investigator assessment) between the two treatment groups using a stratified log-rank test at one-sided 2.5% level of significance
Statistical Test of Hypothesis	p-Value	0.144
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	BKM120 100mg + Fulvestrant, Placebo + Fulvestrant
	Comments	FAS-PI3K pathway activated
	Type of Statistical Test	Other
	Comments	Comparison of overall survival (OS) (based on local investigator assessment) between the two treatment groups using a stratified log-rank test at one-sided 2.5% level of significance
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.61 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BKM120 100mg + Fulvestrant, Placebo + Fulvestrant
	Comments	FAS-PI3K pathway non-activated
	Type of Statistical Test	Other
	Comments	Comparison of overall survival (OS) (based on local investigator assessment) between the two treatment groups using a stratified log-rank test at one-sided 2.5% level of significance
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BKM120 100mg + Fulvestrant, Placebo + Fulvestrant
	Comments	FAS-PI3K pathway unknown
	Type of Statistical Test	Other
	Comments	Comparison of overall survival (OS) (based on local investigator assessment) between the two treatment groups using a stratified log-rank test at one-sided 2.5% level of significance
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.52 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Overall Response Rate (ORR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort
Description	Overall Response Rate (ORR) is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1. ORR was analyzed in the full population. Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target/non target lesions: Complete Response (CR), disappearance of all target/non target lesions (all lymph nodes assigned as non-target lesions must be non-pathological in size (< 10 mm short axis)); Partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions ; Overall Response (OR)= CR+PR. Only descriptive analysis performed.
Time Frame	From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) in the Full Population, the Main Study Cohort (known PI3K pathway activation status [activated, non activated]) and the PI3K unknown cohort (PI3K pathway unknown status) were considered.

Arm/Group Title	BKM120 100mg + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Measure Participants	576	571
FAS-Full population	11.8 2%	7.7 1.3%
FAS-Main cohort	11.0 1.9%	7.8 1.4%
FAS-PI3K pathway activated	10.6 1.8%	8.2 1.4%
FAS-PI3K pathway non-activated	11.3 2%	7.5 1.3%
FAS-PI3K pathway unknown	14.1 2.4%	7.5 1.3%

4. Secondary Outcome

Title	Clinical Benefit Rate (CBR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort
Description	Clinical Benefit Rate (CBR) is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or Non-CR/non-PD lasting more than 24 weeks based on local investigator's assessment according to RECIST 1.1. CBR was analyzed in the full population. Only descriptive analysis performed.
Time Frame	From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) in the Full Population, the Main Study Cohort (known PI3K pathway activation status [activated, non activated]) and the PI3K unknown cohort (PI3K pathway unknown status) were considered.

Arm/Group Title	BKM120 100mg + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Measure Participants	576	571
FAS-Full population	43.8 7.6%	42.0 7.4%
FAS-Main cohort	41.7 7.2%	39.6 6.9%
FAS-PI3K pathway activated	40.4 7%	40.8 7.1%
FAS-PI3K pathway non-activated	42.7 7.4%	38.8 6.8%
FAS-PI3K pathway unknown	49.7 8.6%	49.0 8.6%

5. Secondary Outcome

Title	Number of Participants With On-Treatments Adverse Events, Serious Adverse Events and Deaths
Description	Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths. Only descriptive analysis performed.
Time Frame	From first dose of study treatment to 30 days after last dose of study treatment, assessed for approximately 5 years

Outcome Measure Data

Analysis Population Description

Safety Set (SS) in Full Population

Arm/Group Title	BKM120 100mg + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Measure Participants	573	570
On-treatment Adverse Event (AEs)	569 98.8%	532 93.2%
On-treatment Serious Adverse Event (SAEs)	144 25%	101 17.7%
On-treatment Deaths	12 2.1%	13 2.3%
Primary cause of Death = Study Indication	6 1%	7 1.2%
Primary cause of Death = Unknown reason	2 0.3%	0 0%
Primary cause of Death = Disease Progression	2 0.3%	2 0.4%
Primary cause of Death = Pneumonia	1 0.2%	0 0%
Primary cause of Death = Septic Shock	1 0.2%	0 0%
Primary cause of Death = Cerebral Haemorrhage	0 0%	1 0.2%
Primary cause of Death = Cerebral Accident	0 0%	1 0.2%
Primary cause of Death = Sudden Death	0 0%	1 0.2%
Primary cause of Death = Urosepsis	0 0%	1 0.2%

6. Secondary Outcome

Title	Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 2 Day 1
Description	Plasma samples were collected from the first 200 BKM120-treated patients on Cycle 2 Day 1 (at pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h and 24h [before Cycle 2 Day 2 dose] post-dose). Each cycle is 28 days. Only descriptive analysis performed.
Time Frame	Cycle2 Day1 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours post-dose). Each cycle is 28 days.

Outcome Measure Data

Analysis Population Description

Full Pharmacokinetic Analysis Set (FPAS) included the subset of the patients in the buparlisib PAS who: Received all planned doses of BKM120 100mg + Fulvestrant preceding full PK profile assessment Did not vomit within 4 hours of buparlisib dosing after administration Had an evaluable full PK profile available

Arm/Group Title	BKM120 100mg + Fulvestrant
Arm/Group Description	BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
Measure Participants	35
C2D1 0hr (predose)	768.306 (69.1)
C2D1 0.5hr	750.767 (55.4)
C2D1 1hr	988.341 (49.2)
C2D1 1.5hr	1082.086 (45.0)
C2D1 2hr	1099.517 (36.4)
C2D1 3hr	1081.123 (43.2)
C2D1 4hr	935.485 (43.0)
C2D1 6hr	795.555 (45.1)
C2D1 8hr	808.886 (50.5)
C2D1 24hr	712.336 (52.7)

7. Secondary Outcome

Title	Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS)
Description	Pre-dose samples were collected for trough concentrations at Cycle 2 Day 1, Cycle 2 Day 15 and Cycle 3 Day 1. Each cycle is 28 days. Only descriptive analysis performed.
Time Frame	Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1. Each cycle is 28 days.

Outcome Measure Data

Analysis Population Description

BKM120 Pharmacokinetic Analysis Set or Buparlisib pharmacokinetic analysis set (Buparlisib PAS) included all patients who received at least one dose of study medication buparlisib and had at least one evaluable post-treatment buparlisib concentration measurement.

Arm/Group Title	BKM120 100mg + Fulvestrant
Arm/Group Description	BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.
Measure Participants	93
Cycle 2 Day 1	733.278 (75.6)
Cycle 2 Day 15	735.172 (51.2)
Cycle 3 Day 1	716.414 (84.8)

8. Secondary Outcome

Title	Median Time to Definitive Deterioration of the ECOG Performance Status - Full Analysis Set (FAS)
Description	Time to definitive deterioration of the ECOG PS was defined as the time between the date of randomization and the date of the assessment at which definitive deterioration was seen. Only descriptive analysis performed.
Time Frame	Up to approx 27 months

Outcome Measure Data

Analysis Population Description

Full Analysis (FAS)

Arm/Group Title	BKM120 100mg + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Measure Participants	576	571
Median (95% Confidence Interval) [Months]	24.0	26.4

9. Secondary Outcome

Title	Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30
Description	The global health status/QoL scale score of the QLQ-C30 is identified as the primary PRO variable of interest. Physical Functioning (PF), Emotional Functioning (EF) and Social Functioning (SF) scale scores of the QLQ-C30. The time to definitive 10% deterioration is defined as the time from the randomization date to the date of an event, which is defined as a worsening (decrease) in score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study or death due to any cause. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high /healthy level of functioning, a high score for the global health status / QoL represents a high QoL. Patients were assessed up to approx. 8.3 months. Only descriptive analysis performed.
Time Frame	Cycle 1 day 1, cycle 1 day 15, 6 weeks after randomisation and then every 8 weeks until end of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis (FAS)

Arm/Group Title	BKM120 100mg + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Measure Participants	576	571
Median (95% Confidence Interval) [Months]	7.10	11.50

Adverse Events

Time Frame	Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, assessed for approximately 5 years
Adverse Event Reporting Description	Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up. Maximum exposure to study treatments = 52.9 months (BKM120 100mg + Fulvestrant treatment group) and 69.6 months (Placebo + Fulvestrant treatment group).
Arm/Group Title	BKM120 100 mg + Fulvestrant		Placebo + Fulvestrant
Arm/Group Description	BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.		BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
All Cause Mortality
	BKM120 100 mg + Fulvestrant		Placebo + Fulvestrant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/573 (2.1%)		13/570 (2.3%)
Serious Adverse Events
	BKM120 100 mg + Fulvestrant		Placebo + Fulvestrant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	146/573 (25.5%)		101/570 (17.7%)
Blood and lymphatic system disorders
Anaemia	4/573 (0.7%)		3/570 (0.5%)
Disseminated intravascular coagulation	0/573 (0%)		1/570 (0.2%)
Neutropenia	1/573 (0.2%)		1/570 (0.2%)
Thrombocytopenia	0/573 (0%)		1/570 (0.2%)
Cardiac disorders
Acute coronary syndrome	1/573 (0.2%)		0/570 (0%)
Angina pectoris	1/573 (0.2%)		1/570 (0.2%)
Atrial fibrillation	2/573 (0.3%)		0/570 (0%)
Atrial flutter	0/573 (0%)		1/570 (0.2%)
Cardiac arrest	1/573 (0.2%)		0/570 (0%)
Cardiac failure	0/573 (0%)		1/570 (0.2%)
Cardiac tamponade	0/573 (0%)		1/570 (0.2%)
Pericardial effusion	1/573 (0.2%)		1/570 (0.2%)
Pericarditis	0/573 (0%)		1/570 (0.2%)
Sinus node dysfunction	1/573 (0.2%)		0/570 (0%)
Supraventricular tachycardia	0/573 (0%)		1/570 (0.2%)
Ear and labyrinth disorders
Vertigo	2/573 (0.3%)		2/570 (0.4%)
Eye disorders
Cataract	1/573 (0.2%)		0/570 (0%)
Retinal tear	1/573 (0.2%)		0/570 (0%)
Gastrointestinal disorders
Abdominal pain	2/573 (0.3%)		3/570 (0.5%)
Abdominal pain lower	1/573 (0.2%)		1/570 (0.2%)
Ascites	0/573 (0%)		2/570 (0.4%)
Colitis	1/573 (0.2%)		0/570 (0%)
Constipation	0/573 (0%)		1/570 (0.2%)
Diarrhoea	7/573 (1.2%)		2/570 (0.4%)
Gastric ulcer	0/573 (0%)		1/570 (0.2%)
Gastric ulcer haemorrhage	1/573 (0.2%)		0/570 (0%)
Gastritis	1/573 (0.2%)		1/570 (0.2%)
Gastrointestinal haemorrhage	0/573 (0%)		1/570 (0.2%)
Haematemesis	1/573 (0.2%)		0/570 (0%)
Ileus	1/573 (0.2%)		0/570 (0%)
Intestinal obstruction	0/573 (0%)		1/570 (0.2%)
Nausea	4/573 (0.7%)		2/570 (0.4%)
Obstruction gastric	2/573 (0.3%)		0/570 (0%)
Oesophageal stenosis	1/573 (0.2%)		0/570 (0%)
Oesophagitis	0/573 (0%)		1/570 (0.2%)
Small intestinal obstruction	0/573 (0%)		3/570 (0.5%)
Stomatitis	3/573 (0.5%)		1/570 (0.2%)
Toothache	1/573 (0.2%)		0/570 (0%)
Vomiting	7/573 (1.2%)		5/570 (0.9%)
General disorders
Asthenia	7/573 (1.2%)		2/570 (0.4%)
Breakthrough pain	1/573 (0.2%)		0/570 (0%)
Condition aggravated	1/573 (0.2%)		0/570 (0%)
Death	1/573 (0.2%)		0/570 (0%)
Disease progression	0/573 (0%)		1/570 (0.2%)
Fatigue	7/573 (1.2%)		0/570 (0%)
General physical health deterioration	6/573 (1%)		2/570 (0.4%)
Incarcerated hernia	1/573 (0.2%)		0/570 (0%)
Malaise	0/573 (0%)		1/570 (0.2%)
Non-cardiac chest pain	1/573 (0.2%)		2/570 (0.4%)
Oedema peripheral	1/573 (0.2%)		0/570 (0%)
Pyrexia	3/573 (0.5%)		3/570 (0.5%)
Sudden death	0/573 (0%)		1/570 (0.2%)
Hepatobiliary disorders
Bile duct obstruction	1/573 (0.2%)		0/570 (0%)
Cholelithiasis	0/573 (0%)		1/570 (0.2%)
Drug-induced liver injury	1/573 (0.2%)		0/570 (0%)
Hepatic failure	1/573 (0.2%)		1/570 (0.2%)
Hepatic function abnormal	1/573 (0.2%)		0/570 (0%)
Hepatic pain	1/573 (0.2%)		0/570 (0%)
Hepatitis acute	0/573 (0%)		1/570 (0.2%)
Hepatitis toxic	1/573 (0.2%)		0/570 (0%)
Hepatocellular injury	2/573 (0.3%)		0/570 (0%)
Hepatotoxicity	1/573 (0.2%)		0/570 (0%)
Immune system disorders
Drug hypersensitivity	1/573 (0.2%)		0/570 (0%)
Infections and infestations
Abdominal infection	1/573 (0.2%)		0/570 (0%)
Abscess	1/573 (0.2%)		0/570 (0%)
Breast cellulitis	1/573 (0.2%)		1/570 (0.2%)
Bronchitis	0/573 (0%)		1/570 (0.2%)
Candida sepsis	1/573 (0.2%)		0/570 (0%)
Cellulitis	0/573 (0%)		1/570 (0.2%)
Clostridium difficile colitis	1/573 (0.2%)		1/570 (0.2%)
Clostridium difficile infection	0/573 (0%)		1/570 (0.2%)
Gastroenteritis	3/573 (0.5%)		0/570 (0%)
Gastroenteritis norovirus	1/573 (0.2%)		0/570 (0%)
Infectious colitis	1/573 (0.2%)		0/570 (0%)
Lower respiratory tract infection	2/573 (0.3%)		0/570 (0%)
Lung infection	2/573 (0.3%)		2/570 (0.4%)
Peritonitis	0/573 (0%)		2/570 (0.4%)
Pneumonia	3/573 (0.5%)		5/570 (0.9%)
Pyelonephritis	0/573 (0%)		2/570 (0.4%)
Pyelonephritis acute	1/573 (0.2%)		0/570 (0%)
Pyuria	0/573 (0%)		1/570 (0.2%)
Sepsis	2/573 (0.3%)		1/570 (0.2%)
Septic shock	1/573 (0.2%)		1/570 (0.2%)
Soft tissue infection	0/573 (0%)		1/570 (0.2%)
Tonsillitis	1/573 (0.2%)		0/570 (0%)
Tracheobronchitis	1/573 (0.2%)		0/570 (0%)
Tuberculosis	0/573 (0%)		1/570 (0.2%)
Urinary tract infection	3/573 (0.5%)		1/570 (0.2%)
Urosepsis	1/573 (0.2%)		2/570 (0.4%)
Vestibular neuronitis	0/573 (0%)		1/570 (0.2%)
Viral labyrinthitis	1/573 (0.2%)		0/570 (0%)
Injury, poisoning and procedural complications
Ankle fracture	0/573 (0%)		1/570 (0.2%)
Fall	0/573 (0%)		1/570 (0.2%)
Femur fracture	3/573 (0.5%)		3/570 (0.5%)
Fracture	0/573 (0%)		1/570 (0.2%)
Hip fracture	2/573 (0.3%)		2/570 (0.4%)
Humerus fracture	0/573 (0%)		1/570 (0.2%)
Limb injury	1/573 (0.2%)		0/570 (0%)
Post procedural haemorrhage	0/573 (0%)		1/570 (0.2%)
Pubis fracture	1/573 (0.2%)		0/570 (0%)
Radius fracture	1/573 (0.2%)		0/570 (0%)
Spinal compression fracture	0/573 (0%)		2/570 (0.4%)
Toxicity to various agents	0/573 (0%)		1/570 (0.2%)
Wound dehiscence	1/573 (0.2%)		0/570 (0%)
Wrist fracture	0/573 (0%)		2/570 (0.4%)
Investigations
Alanine aminotransferase increased	17/573 (3%)		1/570 (0.2%)
Aspartate aminotransferase increased	14/573 (2.4%)		1/570 (0.2%)
Blood bilirubin increased	2/573 (0.3%)		1/570 (0.2%)
Blood creatinine increased	2/573 (0.3%)		0/570 (0%)
Ejection fraction decreased	1/573 (0.2%)		0/570 (0%)
Gamma-glutamyltransferase increased	0/573 (0%)		1/570 (0.2%)
Haemoglobin decreased	0/573 (0%)		1/570 (0.2%)
Hepatic enzyme increased	2/573 (0.3%)		0/570 (0%)
Transaminases increased	2/573 (0.3%)		0/570 (0%)
Weight decreased	1/573 (0.2%)		0/570 (0%)
Metabolism and nutrition disorders
Cachexia	1/573 (0.2%)		0/570 (0%)
Decreased appetite	3/573 (0.5%)		0/570 (0%)
Dehydration	5/573 (0.9%)		0/570 (0%)
Diabetes mellitus inadequate control	1/573 (0.2%)		0/570 (0%)
Diabetic ketoacidosis	1/573 (0.2%)		0/570 (0%)
Hypercalcaemia	2/573 (0.3%)		1/570 (0.2%)
Hyperglycaemia	11/573 (1.9%)		0/570 (0%)
Hyperglycaemic hyperosmolar nonketotic syndrome	1/573 (0.2%)		0/570 (0%)
Hypoglycaemia	0/573 (0%)		1/570 (0.2%)
Hypokalaemia	1/573 (0.2%)		0/570 (0%)
Hyponatraemia	1/573 (0.2%)		0/570 (0%)
Malnutrition	1/573 (0.2%)		0/570 (0%)
Type 2 diabetes mellitus	1/573 (0.2%)		0/570 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/573 (0.2%)		3/570 (0.5%)
Back pain	0/573 (0%)		3/570 (0.5%)
Bone pain	0/573 (0%)		1/570 (0.2%)
Joint swelling	0/573 (0%)		1/570 (0.2%)
Muscle spasms	0/573 (0%)		1/570 (0.2%)
Muscular weakness	2/573 (0.3%)		0/570 (0%)
Musculoskeletal chest pain	0/573 (0%)		1/570 (0.2%)
Neck pain	0/573 (0%)		2/570 (0.4%)
Osteonecrosis	0/573 (0%)		1/570 (0.2%)
Pain in extremity	2/573 (0.3%)		0/570 (0%)
Pathological fracture	0/573 (0%)		2/570 (0.4%)
Spinal column stenosis	0/573 (0%)		1/570 (0.2%)
Spinal pain	0/573 (0%)		1/570 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/573 (0.2%)		1/570 (0.2%)
Malignant pleural effusion	1/573 (0.2%)		0/570 (0%)
Metastases to bone	0/573 (0%)		1/570 (0.2%)
Metastases to central nervous system	0/573 (0%)		2/570 (0.4%)
Metastases to meninges	2/573 (0.3%)		0/570 (0%)
Tumour associated fever	0/573 (0%)		1/570 (0.2%)
Tumour pain	1/573 (0.2%)		0/570 (0%)
Nervous system disorders
Cerebral haemorrhage	0/573 (0%)		1/570 (0.2%)
Cerebrovascular accident	0/573 (0%)		3/570 (0.5%)
Coordination abnormal	1/573 (0.2%)		0/570 (0%)
Dementia	1/573 (0.2%)		0/570 (0%)
Depressed level of consciousness	0/573 (0%)		3/570 (0.5%)
Dizziness	1/573 (0.2%)		1/570 (0.2%)
Encephalopathy	1/573 (0.2%)		0/570 (0%)
Headache	1/573 (0.2%)		1/570 (0.2%)
Hypoglycaemic coma	1/573 (0.2%)		0/570 (0%)
Movement disorder	1/573 (0.2%)		0/570 (0%)
Neurological decompensation	0/573 (0%)		1/570 (0.2%)
Peripheral sensorimotor neuropathy	0/573 (0%)		1/570 (0.2%)
Posterior reversible encephalopathy syndrome	1/573 (0.2%)		0/570 (0%)
Sciatica	0/573 (0%)		1/570 (0.2%)
Seizure	1/573 (0.2%)		0/570 (0%)
Spinal cord compression	1/573 (0.2%)		2/570 (0.4%)
Status epilepticus	0/573 (0%)		1/570 (0.2%)
Syncope	1/573 (0.2%)		4/570 (0.7%)
Transient ischaemic attack	0/573 (0%)		1/570 (0.2%)
Tremor	2/573 (0.3%)		0/570 (0%)
Trigeminal neuralgia	0/573 (0%)		1/570 (0.2%)
Vascular dementia	1/573 (0.2%)		0/570 (0%)
Psychiatric disorders
Anxiety	1/573 (0.2%)		1/570 (0.2%)
Confusional state	1/573 (0.2%)		0/570 (0%)
Delirium	1/573 (0.2%)		0/570 (0%)
Depressed mood	0/573 (0%)		1/570 (0.2%)
Depression	4/573 (0.7%)		0/570 (0%)
Disorientation	1/573 (0.2%)		0/570 (0%)
Mental status changes	1/573 (0.2%)		1/570 (0.2%)
Renal and urinary disorders
Acute kidney injury	2/573 (0.3%)		1/570 (0.2%)
Haematuria	0/573 (0%)		1/570 (0.2%)
Hydronephrosis	1/573 (0.2%)		1/570 (0.2%)
Renal failure	1/573 (0.2%)		2/570 (0.4%)
Renal impairment	1/573 (0.2%)		0/570 (0%)
Ureteric obstruction	1/573 (0.2%)		0/570 (0%)
Urinary incontinence	1/573 (0.2%)		0/570 (0%)
Urinary tract obstruction	3/573 (0.5%)		0/570 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/573 (0%)		1/570 (0.2%)
Dyspnoea	4/573 (0.7%)		3/570 (0.5%)
Dyspnoea at rest	0/573 (0%)		1/570 (0.2%)
Pleural effusion	1/573 (0.2%)		8/570 (1.4%)
Pneumonia aspiration	2/573 (0.3%)		0/570 (0%)
Pneumonitis	1/573 (0.2%)		1/570 (0.2%)
Pneumothorax	0/573 (0%)		1/570 (0.2%)
Pulmonary embolism	1/573 (0.2%)		0/570 (0%)
Respiratory failure	0/573 (0%)		1/570 (0.2%)
Skin and subcutaneous tissue disorders
Angioedema	1/573 (0.2%)		0/570 (0%)
Dermatitis	1/573 (0.2%)		0/570 (0%)
Dermatitis exfoliative	1/573 (0.2%)		0/570 (0%)
Drug reaction with eosinophilia and systemic symptoms	2/573 (0.3%)		0/570 (0%)
Palmar-plantar erythrodysaesthesia syndrome	1/573 (0.2%)		0/570 (0%)
Pruritus	1/573 (0.2%)		0/570 (0%)
Rash	3/573 (0.5%)		0/570 (0%)
Rash erythematous	1/573 (0.2%)		0/570 (0%)
Rash maculo-papular	2/573 (0.3%)		0/570 (0%)
Skin toxicity	0/573 (0%)		1/570 (0.2%)
Toxic skin eruption	1/573 (0.2%)		0/570 (0%)
Vascular disorders
Hypertension	1/573 (0.2%)		0/570 (0%)
Venous thrombosis	1/573 (0.2%)		0/570 (0%)
Other (Not Including Serious) Adverse Events
	BKM120 100 mg + Fulvestrant		Placebo + Fulvestrant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	560/573 (97.7%)		485/570 (85.1%)
Blood and lymphatic system disorders
Anaemia	38/573 (6.6%)		51/570 (8.9%)
Gastrointestinal disorders
Abdominal pain	40/573 (7%)		30/570 (5.3%)
Abdominal pain upper	46/573 (8%)		38/570 (6.7%)
Constipation	68/573 (11.9%)		71/570 (12.5%)
Diarrhoea	198/573 (34.6%)		84/570 (14.7%)
Dry mouth	46/573 (8%)		20/570 (3.5%)
Dyspepsia	52/573 (9.1%)		25/570 (4.4%)
Nausea	227/573 (39.6%)		138/570 (24.2%)
Stomatitis	124/573 (21.6%)		40/570 (7%)
Vomiting	92/573 (16.1%)		79/570 (13.9%)
General disorders
Asthenia	113/573 (19.7%)		62/570 (10.9%)
Fatigue	187/573 (32.6%)		143/570 (25.1%)
Injection site pain	27/573 (4.7%)		34/570 (6%)
Oedema peripheral	38/573 (6.6%)		30/570 (5.3%)
Pyrexia	44/573 (7.7%)		22/570 (3.9%)
Infections and infestations
Upper respiratory tract infection	29/573 (5.1%)		31/570 (5.4%)
Urinary tract infection	46/573 (8%)		31/570 (5.4%)
Investigations
Alanine aminotransferase increased	229/573 (40%)		39/570 (6.8%)
Aspartate aminotransferase increased	217/573 (37.9%)		55/570 (9.6%)
Blood alkaline phosphatase increased	40/573 (7%)		31/570 (5.4%)
Gamma-glutamyltransferase increased	45/573 (7.9%)		39/570 (6.8%)
Weight decreased	84/573 (14.7%)		24/570 (4.2%)
Metabolism and nutrition disorders
Decreased appetite	174/573 (30.4%)		68/570 (11.9%)
Hyperglycaemia	244/573 (42.6%)		46/570 (8.1%)
Hypokalaemia	41/573 (7.2%)		13/570 (2.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	62/573 (10.8%)		74/570 (13%)
Back pain	66/573 (11.5%)		72/570 (12.6%)
Bone pain	38/573 (6.6%)		34/570 (6%)
Muscle spasms	32/573 (5.6%)		21/570 (3.7%)
Musculoskeletal pain	27/573 (4.7%)		40/570 (7%)
Pain in extremity	51/573 (8.9%)		61/570 (10.7%)
Nervous system disorders
Dizziness	75/573 (13.1%)		30/570 (5.3%)
Dysgeusia	84/573 (14.7%)		22/570 (3.9%)
Headache	88/573 (15.4%)		79/570 (13.9%)
Tremor	44/573 (7.7%)		7/570 (1.2%)
Psychiatric disorders
Anxiety	129/573 (22.5%)		53/570 (9.3%)
Depression	152/573 (26.5%)		56/570 (9.8%)
Insomnia	60/573 (10.5%)		50/570 (8.8%)
Mood altered	40/573 (7%)		17/570 (3%)
Respiratory, thoracic and mediastinal disorders
Cough	76/573 (13.3%)		69/570 (12.1%)
Dyspnoea	44/573 (7.7%)		56/570 (9.8%)
Skin and subcutaneous tissue disorders
Alopecia	41/573 (7.2%)		20/570 (3.5%)
Dry skin	69/573 (12%)		17/570 (3%)
Pruritus	88/573 (15.4%)		33/570 (5.8%)
Rash	187/573 (32.6%)		39/570 (6.8%)
Rash maculo-papular	39/573 (6.8%)		8/570 (1.4%)
Vascular disorders
Hot flush	33/573 (5.8%)		53/570 (9.3%)
Hypertension	57/573 (9.9%)		29/570 (5.1%)

Limitations/Caveats

Novartis made the decision not to pursue further development of buparlisib and to terminate the ongoing studies in Breast Cancer. The CBKM120F2302 study was terminated on 19-Apr-2019 (last subject last visit).

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.