Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer Who Have Progressed on or After Prior Treatments (BYLieve)

• ClinicalTrials.gov Identifier: NCT03056755
• Recruitment Status: Active, not recruiting
• First Posted: February 17, 2017
• Results First Posted: March 27, 2024
• Last Update Posted: March 27, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer
• Interventions: Drug: Alpelisib; Drug: Fulvestrant; Drug: Letrozole; Drug: Goserelin; Drug: Leuprolide
• Enrollment: 379

Participant Flow

Recruitment Details	This study was conducted in 92 centers across 19 countries
Pre-assignment Details	Screening assessments occurred before 21 days of the start of treatment. Participant flow table provides data as of 29-Jul-2022 (end of Core Phase).

Arm/Group Title	Cohort A: Pre-treated With CDK 4/6i + AI	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant	Cohort C: Pre-treated With Systemic Chemotherapy or ET
Arm/Group Description	Participants who received any CDK 4/6i plus AI as immediate prior treatment will receive alpelisib + fulvestrant	Patients who received any CDK 4/6i plus fulvestrant as immediate prior treatment will receive alpelisib + letrozole	Participants who received systemic chemotherapy or endocrine therapy (ET) (as monotherapy or in combination with targeted treatment except CDK 4/6i + AI) as immediate prior treatment will receive alpelisib + fulvestrant.
Period Title: Treatment- Core Phase
Started	127	126	126
Completed	1	0	10
Not Completed	126	126	116
Reason Not Completed
Progressive disease	89	88	90
Adverse Event	20	14	13
Physician Decision	7	13	5
Subject/guardian decision	5	8	4
Death	3	2	4
Protocol deviation	1	1	0
Technical problems	1	0	0
Period Title: Post-treatment Efficacy - Core Phase
Started	14	14	7
Completed	0	0	0
Not Completed	14	14	7
Reason Not Completed
On-going at the time of the data cut-off date (29-Jul-2022)	1	1	2
Progressive disease	11	9	5
Adverse Event	1	1	0
Death	1	3	0

Baseline Characteristics

Arm/Group Title		Cohort A: Pre-treated With CDK 4/6i + AI	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant	Cohort C: Pre-treated With Systemic Chemotherapy or ET	Total
Arm/Group Description		Participants who received any CDK 4/6i plus AI as immediate prior treatment will receive alpelisib + fulvestrant	Patients who received any CDK 4/6i plus fulvestrant as immediate prior treatment will receive alpelisib + letrozole	Participants who received systemic chemotherapy or ET (as monotherapy or in combination with targeted treatment except CDK 4/6i + AI) as immediate prior treatment will receive alpelisib + fulvestrant.	Total of all reporting groups
Overall Number of Baseline Participants		127	126	126	379
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	127 participants	126 participants	126 participants	379 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	95 74.8%	80 63.5%	83 65.9%	258 68.1%
	>=65 years	32 25.2%	46 36.5%	43 34.1%	121 31.9%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	127 participants	126 participants	126 participants	379 participants
	Female	127 100.0%	126 100.0%	125 99.2%	378 99.7%
	Male	0 0.0%	0 0.0%	1 0.8%	1 0.3%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	127 participants	126 participants	126 participants	379 participants
	Caucasian	81 63.8%	85 67.5%	83 65.9%	249 65.7%
	Unknown	23 18.1%	24 19.0%	11 8.7%	58 15.3%
	Asian	12 9.4%	8 6.3%	28 22.2%	48 12.7%
	Black	6 4.7%	1 0.8%	1 0.8%	8 2.1%
	Other	3 2.4%	7 5.6%	3 2.4%	13 3.4%
	Pacific islander	1 0.8%	0 0.0%	0 0.0%	1 0.3%
	Missing	1 0.8%	1 0.8%	0 0.0%	2 0.5%

Outcome Measures

1. Primary Outcome

Title	Core Phase: Percentage of Participants Who Were Alive Without Disease Progression at 6 Months
Description	Percentage of participants who were alive without disease progression at 6-month follow-up based on local investigator assessment per RECIST v1.1 in Cohort A, Cohort B and Cohort C. Participants who progressed, died, or discontinued study before 6 months were counted as a failure.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

Subjects who have been assigned and received at least one dose of the study treatment. They must have a confirmed PI3KCA mutation from a Novartis designated laboratory.

Arm/Group Title	Cohort A: Pre-treated With CDK 4/6i + AI	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant	Cohort C: Pre-treated With Systemic Chemotherapy or ET
Arm/Group Description:	Participants who received any CDK 4/6i plus AI as immediate prior treatment will receive alpelisib + fulvestrant	Patients who received any CDK 4/6i plus fulvestrant as immediate prior treatment will receive alpelisib + letrozole	Participants who received systemic chemotherapy or ET (as monotherapy or in combination with targeted treatment except CDK 4/6i + AI) as immediate prior treatment will receive alpelisib + fulvestrant.
Overall Number of Participants Analyzed	119	114	115
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	53.8; (44.41 to 62.96)	46.5; (37.10 to 56.07)	53.0; (43.51 to 62.41)

2. Secondary Outcome

Title	Core Phase: Progression Free Survival (PFS)
Description	PFS is defined as the time from the date of first dose of study medication to the date of the first documented progression or death due to any cause occurring in the study. PFS was assessed based on local investigator's assessment according to RECIST v1.1. PFS was censored if no PFS event was observed before the cut-off date. The censoring date was the date of last adequate tumor assessment before the cut-off date. If a PFS event was observed after two or more missing or non-adequate tumor assessments, then PFS was censored at the last adequate tumor assessment. PFS was estimated using the Kaplan-Meier method.
Time Frame	From date of first dose to date of first documented progression or death, up to 46 months

Outcome Measure Data

Analysis Population Description

Subjects who have been assigned and received at least one dose of the study treatment. They must have a confirmed PI3KCA mutation from a Novartis designated laboratory.

Arm/Group Title	Cohort A: Pre-treated With CDK 4/6i + AI	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant	Cohort C: Pre-treated With Systemic Chemotherapy or ET
Arm/Group Description:	Participants who received any CDK 4/6i plus AI as immediate prior treatment will receive alpelisib + fulvestrant	Patients who received any CDK 4/6i plus fulvestrant as immediate prior treatment will receive alpelisib + letrozole	Participants who received systemic chemotherapy or ET (as monotherapy or in combination with targeted treatment except CDK 4/6i + AI) as immediate prior treatment will receive alpelisib + fulvestrant.
Overall Number of Participants Analyzed	119	114	115
Median (95% Confidence Interval); Unit of Measure: Months
	8.0; (5.6 to 8.6)	5.6; (3.7 to 7.1)	5.6; (5.4 to 8.1)

3. Secondary Outcome

Title	Core Phase: Progression Free Survival on Next Line Treatment (PFS2)
Description	PFS2 is defined as time from the date of first dose of study medication to the date of first documented progression on next-line therapy or death from any cause. The first documented progression on next-line treatment is based on investigator assessment of progressive disease. PFS2 was estimated using the Kaplan-Meier method.
Time Frame	From date of first dose to date of first documented progression on next-line therapy or death, up to approximately 55 months

Outcome Measure Data

Analysis Population Description

Subjects who have been assigned and received at least one dose of the study treatment. They must have a confirmed PI3KCA mutation from a Novartis designated laboratory.

Arm/Group Title	Cohort A: Pre-treated With CDK 4/6i + AI	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant	Cohort C: Pre-treated With Systemic Chemotherapy or ET
Arm/Group Description:	Participants who received any CDK 4/6i plus AI as immediate prior treatment will receive alpelisib + fulvestrant	Patients who received any CDK 4/6i plus fulvestrant as immediate prior treatment will receive alpelisib + letrozole	Participants who received systemic chemotherapy or ET (as monotherapy or in combination with targeted treatment except CDK 4/6i + AI) as immediate prior treatment will receive alpelisib + fulvestrant.
Overall Number of Participants Analyzed	119	114	115
Median (95% Confidence Interval); Unit of Measure: Months
	15.2; (11.4 to 21.7)	13.0; (10.2 to 13.9)	13.5; (11.5 to 17.3)

4. Secondary Outcome

Title	Core Phase: Overall Response Rate (ORR)
Description	ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST v1.1 in each cohort. CR: Disappearance of all non-nodal target lesions and all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm and all lymph nodes assigned as non-target lesions must be non-pathological in size (<10 mm short axis) PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time Frame	Up to 46 months

Outcome Measure Data

Analysis Population Description

Subjects who have been assigned and received at least one dose of the study treatment. They must have a confirmed PI3KCA mutation from a Novartis designated laboratory.

Arm/Group Title	Cohort A: Pre-treated With CDK 4/6i + AI	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant	Cohort C: Pre-treated With Systemic Chemotherapy or ET
Arm/Group Description:	Participants who received any CDK 4/6i plus AI as immediate prior treatment will receive alpelisib + fulvestrant	Patients who received any CDK 4/6i plus fulvestrant as immediate prior treatment will receive alpelisib + letrozole	Participants who received systemic chemotherapy or ET (as monotherapy or in combination with targeted treatment except CDK 4/6i + AI) as immediate prior treatment will receive alpelisib + fulvestrant.
Overall Number of Participants Analyzed	119	114	115
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	19.3; (12.7 to 27.6)	17.5; (11.1 to 25.8)	25.2; (17.6 to 34.2)

5. Secondary Outcome

Title	Core Phase: Clinical Benefit Rate (CBR)
Description	CBR is defined as the percentage of participants with a BOR of CR or PR or an overall lesion response of stable disease (SD) or Non-CR/ Non-PD lasting ≥ 24 weeks based on local investigator's assessment according to RECIST v1.1. CR: Disappearance of all non-nodal target lesions and all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm and all lymph nodes assigned as non-target lesions must be non-pathological in size (<10 mm short axis) PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Time Frame	Up to 46 months

Outcome Measure Data

Analysis Population Description

Subjects who have been assigned and received at least one dose of the study treatment. They must have a confirmed PI3KCA mutation from a Novartis designated laboratory.

Arm/Group Title	Cohort A: Pre-treated With CDK 4/6i + AI	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant	Cohort C: Pre-treated With Systemic Chemotherapy or ET
Arm/Group Description:	Participants who received any CDK 4/6i plus AI as immediate prior treatment will receive alpelisib + fulvestrant	Patients who received any CDK 4/6i plus fulvestrant as immediate prior treatment will receive alpelisib + letrozole	Participants who received systemic chemotherapy or ET (as monotherapy or in combination with targeted treatment except CDK 4/6i + AI) as immediate prior treatment will receive alpelisib + fulvestrant.
Overall Number of Participants Analyzed	119	114	115
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	46.2; (37.0 to 55.6)	35.1; (26.4 to 44.6)	38.3; (29.4 to 47.8)

6. Secondary Outcome

Title	Core Phase: Duration of Response (DOR)
Description	DOR is the time from the date of first documented response (confirmed CR or PR based on local investigator's assessment according to RECIST v1.1) to the date of first documented progression or death due to underlying cancer. Subjects continuing without progression or death due to underlying cancer were censored at the date of their last adequate tumor assessment. DOR was estimated using the Kaplan-Meier method.
Time Frame	From date of first documented response to first documented progression or death, up to 33.3 months

Outcome Measure Data

Analysis Population Description

Subjects who have been assigned and received at least one dose of the study treatment. They must have a confirmed PI3KCA mutation from a Novartis designated laboratory. Additionally, subjects must have a confirmed CR or PR.

Arm/Group Title	Cohort A: Pre-treated With CDK 4/6i + AI	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant	Cohort C: Pre-treated With Systemic Chemotherapy or ET
Arm/Group Description:	Participants who received any CDK 4/6i plus AI as immediate prior treatment will receive alpelisib + fulvestrant	Patients who received any CDK 4/6i plus fulvestrant as immediate prior treatment will receive alpelisib + letrozole	Participants who received systemic chemotherapy or ET (as monotherapy or in combination with targeted treatment except CDK 4/6i + AI) as immediate prior treatment will receive alpelisib + fulvestrant.
Overall Number of Participants Analyzed	23	20	29
Median (95% Confidence Interval); Unit of Measure: Months
	13.8; (5.5 to 19.4)	6.5; (5.4 to 9.4)	16.5; (8.3 to 22.2)

7. Secondary Outcome

Title	Core Phase: Overall Survival (OS)
Description	OS is defined as the time of start of treatment to date of death or lost to follow-up. If a subject was not known to have died, then the OS data was censored at the date of the last known alive status for the patient.
Time Frame	From date of first dose and up to approximately 55 months

Outcome Measure Data

Analysis Population Description

Subjects who have been assigned and received at least one dose of the study treatment. They must have a confirmed PI3KCA mutation from a Novartis designated laboratory.

Arm/Group Title	Cohort A: Pre-treated With CDK 4/6i + AI	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant	Cohort C: Pre-treated With Systemic Chemotherapy or ET
Arm/Group Description:	Participants who received any CDK 4/6i plus AI as immediate prior treatment will receive alpelisib + fulvestrant	Patients who received any CDK 4/6i plus fulvestrant as immediate prior treatment will receive alpelisib + letrozole	Participants who received systemic chemotherapy or ET (as monotherapy or in combination with targeted treatment except CDK 4/6i + AI) as immediate prior treatment will receive alpelisib + fulvestrant.
Overall Number of Participants Analyzed	119	114	115
Median (95% Confidence Interval); Unit of Measure: Months
	27.3; (21.3 to 32.7)	29.0; (24.5 to 34.8)	20.7; (16.9 to 28.1)

8. Secondary Outcome

Title	Extension Phase: Percentage of Participants With Clinical Benefit as Assessed by the Investigator During the Extension Phase
Description	Percentage of participants with clinical benefit as assessed by the Investigator at scheduled visits during the extension phase
Time Frame	From end of core phase up to 12 months

Outcome Measure Data Not Reported

9. Post-Hoc Outcome

Title	Core Phase: All Collected Deaths
Description	On-treatment deaths in the Core Phase were collected from first dose of treatment up to 30 days after last dose of treatment (for participants who did not enter the Extension Phase) or last treatment (for participants who entered the Extension Phase). Post-treatment survival follow-up deaths in the Core Phase were collected from 31 days after last dose of treatment up to end of Core Phase
Time Frame	On-treatment (Core Phase): up to approximately 43 months. Post-treatment survival (Core Phase): up to approximately 55 months

Outcome Measure Data

Analysis Population Description

Subjects who have been assigned and received at least one dose of the study treatment.

Arm/Group Title		Cohort A: Pre-treated With CDK 4/6i + AI	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant	Cohort C: Pre-treated With Systemic Chemotherapy or ET
Arm/Group Description:		Participants who received any CDK 4/6i plus AI as immediate prior treatment will receive alpelisib + fulvestrant	Patients who received any CDK 4/6i plus fulvestrant as immediate prior treatment will receive alpelisib + letrozole	Participants who received systemic chemotherapy or ET (as monotherapy or in combination with targeted treatment except CDK 4/6i + AI) as immediate prior treatment will receive alpelisib + fulvestrant.
Overall Number of Participants Analyzed		127	126	126
Measure Type: Number; Unit of Measure: Participants
On-treatment (Core Phase)	Number Analyzed	127 participants	126 participants	126 participants
		7	10	8
Post-treatment survival follow-up (Core Phase)	Number Analyzed	107 participants	113 participants	108 participants
		71	66	59
All deaths (Core Phase)	Number Analyzed	127 participants	126 participants	126 participants
		78	76	67

Adverse Events

Time Frame	On-treatment- Core phase: from first treatment to 30 days post-treatment or last treatment in the Core phase (for Extension Phase participants), up to approximately 43 months. Post-treatment survival- Core phase: from 31 days post-treatment in the Core phase to end of Core Phase, up to approximately 55 months;
Adverse Event Reporting Description	Deaths in the post treatment follow-up period are not counted as Adverse Events. The total number at risk in the post treatment survival includes patients that entered the post-treatment survival follow-up period
Arm/Group Title	Cohort A: Pre-treated With CDK 4/6i + AI (On-treatment- Core Phase)	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant (On-treatment- Core Phase)	Cohort C: Pre-treated With Systemic Chemotherapy or ET (On-treatment- Core Phase)	Cohort A: Pre-treated With CDK 4/6i + AI (Post-treatment Survival Follow-up- Core Phase)	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant (Post-treatment Survival Follow-up- Core Phase)	Cohort C:Pre-treated With Systemic Chemotherapy or ET (Post-treatment Survival Follow-up-Core Phase)
Arm/Group Description	AEs collected in the on-treatment period of the core phase (up to 30 days after last treatment for participants who did not enter the Extension Phase or up to last treatment in the Core phase for participants who entered the Extension phase)	AEs collected in the on-treatment period of the core phase (up to 30 days after last treatment for participants who did not enter the Extension phase or up to last treatment in the Core phase for participants who entered the Extension phase)	AEs collected in the on-treatment period of the core phase (up to 30 days after last treatment for participants who did not enter the Extension phase or up to last treatment in the Core phase for participants who entered the Extension phase)	Deaths collected in the post-treatment survival follow-up period (starting from 31 days post-treatment) in the Core phase. No AEs were collected during this period	Deaths collected in the post-treatment survival follow-up period (starting from 31 days post-treatment) in the Core phase. No AEs were collected during this period	Deaths collected in the post-treatment survival follow-up period (starting from 31 days post-treatment) in the Core phase. No AEs were collected during this period
All-Cause Mortality
	Cohort A: Pre-treated With CDK 4/6i + AI (On-treatment- Core Phase)	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant (On-treatment- Core Phase)	Cohort C: Pre-treated With Systemic Chemotherapy or ET (On-treatment- Core Phase)	Cohort A: Pre-treated With CDK 4/6i + AI (Post-treatment Survival Follow-up- Core Phase)	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant (Post-treatment Survival Follow-up- Core Phase)	Cohort C:Pre-treated With Systemic Chemotherapy or ET (Post-treatment Survival Follow-up-Core Phase)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	7/127 (5.51%)	10/126 (7.94%)	8/126 (6.35%)	71/107 (66.36%)	66/113 (58.41%)	59/108 (54.63%)
Serious Adverse Events
	Cohort A: Pre-treated With CDK 4/6i + AI (On-treatment- Core Phase)	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant (On-treatment- Core Phase)	Cohort C: Pre-treated With Systemic Chemotherapy or ET (On-treatment- Core Phase)	Cohort A: Pre-treated With CDK 4/6i + AI (Post-treatment Survival Follow-up- Core Phase)	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant (Post-treatment Survival Follow-up- Core Phase)	Cohort C:Pre-treated With Systemic Chemotherapy or ET (Post-treatment Survival Follow-up-Core Phase)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	37/127 (29.13%)	48/126 (38.10%)	38/126 (30.16%)	0/0	0/0	0/0
Blood and lymphatic system disorders
Anaemia † 1	1/127 (0.79%)	1/126 (0.79%)	1/126 (0.79%)	/0	/0	/0
Febrile neutropenia † 1	1/127 (0.79%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Cardiac disorders
Acute myocardial infarction † 1	1/127 (0.79%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Pericardial effusion † 1	1/127 (0.79%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Supraventricular tachycardia † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Eye disorders
Vision blurred † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Gastrointestinal disorders
Abdominal pain † 1	2/127 (1.57%)	4/126 (3.17%)	0/126 (0.00%)	/0	/0	/0
Ascites † 1	0/127 (0.00%)	1/126 (0.79%)	2/126 (1.59%)	/0	/0	/0
Colitis † 1	1/127 (0.79%)	2/126 (1.59%)	0/126 (0.00%)	/0	/0	/0
Colitis ulcerative † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Diarrhoea † 1	1/127 (0.79%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Duodenal obstruction † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Dysphagia † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Enteritis † 1	0/127 (0.00%)	1/126 (0.79%)	1/126 (0.79%)	/0	/0	/0
Enterocolitis † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Erosive oesophagitis † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Haematemesis † 1	2/127 (1.57%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Intestinal perforation † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Mesenteric artery thrombosis † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Nausea † 1	0/127 (0.00%)	1/126 (0.79%)	1/126 (0.79%)	/0	/0	/0
Subileus † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Vomiting † 1	0/127 (0.00%)	2/126 (1.59%)	2/126 (1.59%)	/0	/0	/0
General disorders
Asthenia † 1	1/127 (0.79%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Fatigue † 1	0/127 (0.00%)	2/126 (1.59%)	0/126 (0.00%)	/0	/0	/0
General physical health deterioration † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Influenza like illness † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Performance status decreased † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Pyrexia † 1	1/127 (0.79%)	2/126 (1.59%)	2/126 (1.59%)	/0	/0	/0
Sudden death † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Hepatobiliary disorders
Biliary obstruction † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Hepatic failure † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Immune system disorders
Anaphylactic reaction † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Hypersensitivity † 1	0/127 (0.00%)	1/126 (0.79%)	1/126 (0.79%)	/0	/0	/0
Infections and infestations
Bacterial infection † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
COVID-19 † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Device related infection † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Escherichia urinary tract infection † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Meningitis † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Pharyngitis † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Pneumonia † 1	1/127 (0.79%)	4/126 (3.17%)	2/126 (1.59%)	/0	/0	/0
Pyelonephritis † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Pyelonephritis acute † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Sepsis † 1	0/127 (0.00%)	2/126 (1.59%)	2/126 (1.59%)	/0	/0	/0
Septic shock † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Urinary tract infection † 1	0/127 (0.00%)	0/126 (0.00%)	2/126 (1.59%)	/0	/0	/0
Wound infection † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Injury, poisoning and procedural complications
Ankle fracture † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Hip fracture † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Procedural pneumothorax † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Thoracic vertebral fracture † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Toxicity to various agents † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Investigations
Alanine aminotransferase increased † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Aspartate aminotransferase increased † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Blood alkaline phosphatase increased † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Blood bilirubin increased † 1	0/127 (0.00%)	1/126 (0.79%)	1/126 (0.79%)	/0	/0	/0
Blood creatine phosphokinase increased † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Laboratory test abnormal † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Liver function test abnormal † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Metabolism and nutrition disorders
Dehydration † 1	1/127 (0.79%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Hypercalcaemia † 1	0/127 (0.00%)	2/126 (1.59%)	2/126 (1.59%)	/0	/0	/0
Hyperglycaemia † 1	7/127 (5.51%)	3/126 (2.38%)	2/126 (1.59%)	/0	/0	/0
Hypokalaemia † 1	0/127 (0.00%)	0/126 (0.00%)	2/126 (1.59%)	/0	/0	/0
Hyponatraemia † 1	1/127 (0.79%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/127 (0.79%)	3/126 (2.38%)	1/126 (0.79%)	/0	/0	/0
Back pain † 1	0/127 (0.00%)	0/126 (0.00%)	3/126 (2.38%)	/0	/0	/0
Musculoskeletal chest pain † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Myalgia † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Osteonecrosis of jaw † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Spinal pain † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Angiosarcoma † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Cancer pain † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Malignant pleural effusion † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Small cell lung cancer † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Tumour associated fever † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Nervous system disorders
Cerebral ischaemia † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Cerebrovascular accident † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Migraine with aura † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Monoparesis † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Psychiatric disorders
Confusional state † 1	0/127 (0.00%)	1/126 (0.79%)	1/126 (0.79%)	/0	/0	/0
Psychotic disorder † 1	1/127 (0.79%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Suicidal ideation † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Renal and urinary disorders
Acute kidney injury † 1	0/127 (0.00%)	3/126 (2.38%)	1/126 (0.79%)	/0	/0	/0
Hydronephrosis † 1	0/127 (0.00%)	1/126 (0.79%)	1/126 (0.79%)	/0	/0	/0
Nephrolithiasis † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Urinary retention † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Urinary tract obstruction † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Atelectasis † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Dyspnoea † 1	3/127 (2.36%)	2/126 (1.59%)	1/126 (0.79%)	/0	/0	/0
Haemothorax † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
Hypoxia † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Pleural effusion † 1	3/127 (2.36%)	2/126 (1.59%)	2/126 (1.59%)	/0	/0	/0
Pneumonitis † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Pneumothorax † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Pulmonary embolism † 1	0/127 (0.00%)	0/126 (0.00%)	1/126 (0.79%)	/0	/0	/0
Respiratory failure † 1	0/127 (0.00%)	2/126 (1.59%)	0/126 (0.00%)	/0	/0	/0
Skin and subcutaneous tissue disorders
Drug reaction with eosinophilia and systemic symptoms † 1	1/127 (0.79%)	0/126 (0.00%)	0/126 (0.00%)	/0	/0	/0
Rash † 1	1/127 (0.79%)	1/126 (0.79%)	2/126 (1.59%)	/0	/0	/0
Rash maculo-papular † 1	3/127 (2.36%)	2/126 (1.59%)	1/126 (0.79%)	/0	/0	/0
Skin ulcer † 1	0/127 (0.00%)	2/126 (1.59%)	0/126 (0.00%)	/0	/0	/0
Vascular disorders
Deep vein thrombosis † 1	0/127 (0.00%)	1/126 (0.79%)	0/126 (0.00%)	/0	/0	/0
1 Term from vocabulary, MedDRA (25.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Cohort A: Pre-treated With CDK 4/6i + AI (On-treatment- Core Phase)	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant (On-treatment- Core Phase)	Cohort C: Pre-treated With Systemic Chemotherapy or ET (On-treatment- Core Phase)	Cohort A: Pre-treated With CDK 4/6i + AI (Post-treatment Survival Follow-up- Core Phase)	Cohort B: Pre-treated With CDK 4/6i + Fulvestrant (Post-treatment Survival Follow-up- Core Phase)	Cohort C:Pre-treated With Systemic Chemotherapy or ET (Post-treatment Survival Follow-up-Core Phase)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	126/127 (99.21%)	126/126 (100.00%)	123/126 (97.62%)	0/0	0/0	0/0
Blood and lymphatic system disorders
Anaemia † 1	11/127 (8.66%)	9/126 (7.14%)	9/126 (7.14%)	/0	/0	/0
Neutropenia † 1	5/127 (3.94%)	3/126 (2.38%)	7/126 (5.56%)	/0	/0	/0
Eye disorders
Dry eye † 1	7/127 (5.51%)	6/126 (4.76%)	5/126 (3.97%)	/0	/0	/0
Vision blurred † 1	10/127 (7.87%)	4/126 (3.17%)	6/126 (4.76%)	/0	/0	/0
Gastrointestinal disorders
Abdominal pain † 1	17/127 (13.39%)	21/126 (16.67%)	10/126 (7.94%)	/0	/0	/0
Abdominal pain upper † 1	16/127 (12.60%)	17/126 (13.49%)	6/126 (4.76%)	/0	/0	/0
Constipation † 1	12/127 (9.45%)	16/126 (12.70%)	15/126 (11.90%)	/0	/0	/0
Diarrhoea † 1	82/127 (64.57%)	86/126 (68.25%)	68/126 (53.97%)	/0	/0	/0
Dry mouth † 1	11/127 (8.66%)	10/126 (7.94%)	11/126 (8.73%)	/0	/0	/0
Dyspepsia † 1	19/127 (14.96%)	13/126 (10.32%)	13/126 (10.32%)	/0	/0	/0
Nausea † 1	59/127 (46.46%)	68/126 (53.97%)	51/126 (40.48%)	/0	/0	/0
Stomatitis † 1	34/127 (26.77%)	43/126 (34.13%)	38/126 (30.16%)	/0	/0	/0
Vomiting † 1	31/127 (24.41%)	31/126 (24.60%)	31/126 (24.60%)	/0	/0	/0
General disorders
Asthenia † 1	24/127 (18.90%)	27/126 (21.43%)	15/126 (11.90%)	/0	/0	/0
Fatigue † 1	39/127 (30.71%)	38/126 (30.16%)	44/126 (34.92%)	/0	/0	/0
Oedema peripheral † 1	10/127 (7.87%)	12/126 (9.52%)	8/126 (6.35%)	/0	/0	/0
Pyrexia † 1	17/127 (13.39%)	19/126 (15.08%)	19/126 (15.08%)	/0	/0	/0
Infections and infestations
Conjunctivitis † 1	1/127 (0.79%)	2/126 (1.59%)	7/126 (5.56%)	/0	/0	/0
Nasopharyngitis † 1	9/127 (7.09%)	4/126 (3.17%)	3/126 (2.38%)	/0	/0	/0
Upper respiratory tract infection † 1	5/127 (3.94%)	8/126 (6.35%)	2/126 (1.59%)	/0	/0	/0
Urinary tract infection † 1	14/127 (11.02%)	11/126 (8.73%)	15/126 (11.90%)	/0	/0	/0
Investigations
Alanine aminotransferase increased † 1	13/127 (10.24%)	13/126 (10.32%)	18/126 (14.29%)	/0	/0	/0
Aspartate aminotransferase increased † 1	17/127 (13.39%)	11/126 (8.73%)	15/126 (11.90%)	/0	/0	/0
Blood alkaline phosphatase increased † 1	5/127 (3.94%)	7/126 (5.56%)	3/126 (2.38%)	/0	/0	/0
Blood creatinine increased † 1	15/127 (11.81%)	12/126 (9.52%)	8/126 (6.35%)	/0	/0	/0
Gamma-glutamyltransferase increased † 1	7/127 (5.51%)	7/126 (5.56%)	2/126 (1.59%)	/0	/0	/0
Glycosylated haemoglobin increased † 1	3/127 (2.36%)	8/126 (6.35%)	2/126 (1.59%)	/0	/0	/0
Weight decreased † 1	18/127 (14.17%)	19/126 (15.08%)	23/126 (18.25%)	/0	/0	/0
Metabolism and nutrition disorders
Decreased appetite † 1	37/127 (29.13%)	56/126 (44.44%)	42/126 (33.33%)	/0	/0	/0
Hyperglycaemia † 1	76/127 (59.84%)	81/126 (64.29%)	85/126 (67.46%)	/0	/0	/0
Hypokalaemia † 1	10/127 (7.87%)	12/126 (9.52%)	8/126 (6.35%)	/0	/0	/0
Hyponatraemia † 1	9/127 (7.09%)	3/126 (2.38%)	1/126 (0.79%)	/0	/0	/0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	19/127 (14.96%)	21/126 (16.67%)	14/126 (11.11%)	/0	/0	/0
Back pain † 1	10/127 (7.87%)	14/126 (11.11%)	12/126 (9.52%)	/0	/0	/0
Bone pain † 1	6/127 (4.72%)	5/126 (3.97%)	8/126 (6.35%)	/0	/0	/0
Muscle spasms † 1	14/127 (11.02%)	15/126 (11.90%)	14/126 (11.11%)	/0	/0	/0
Musculoskeletal chest pain † 1	8/127 (6.30%)	3/126 (2.38%)	6/126 (4.76%)	/0	/0	/0
Myalgia † 1	10/127 (7.87%)	6/126 (4.76%)	5/126 (3.97%)	/0	/0	/0
Pain in extremity † 1	5/127 (3.94%)	7/126 (5.56%)	7/126 (5.56%)	/0	/0	/0
Nervous system disorders
Dizziness † 1	8/127 (6.30%)	9/126 (7.14%)	7/126 (5.56%)	/0	/0	/0
Dysgeusia † 1	18/127 (14.17%)	21/126 (16.67%)	8/126 (6.35%)	/0	/0	/0
Headache † 1	28/127 (22.05%)	25/126 (19.84%)	21/126 (16.67%)	/0	/0	/0
Psychiatric disorders
Insomnia † 1	6/127 (4.72%)	3/126 (2.38%)	9/126 (7.14%)	/0	/0	/0
Respiratory, thoracic and mediastinal disorders
Cough † 1	14/127 (11.02%)	9/126 (7.14%)	13/126 (10.32%)	/0	/0	/0
Dyspnoea † 1	19/127 (14.96%)	14/126 (11.11%)	7/126 (5.56%)	/0	/0	/0
Oropharyngeal pain † 1	6/127 (4.72%)	5/126 (3.97%)	7/126 (5.56%)	/0	/0	/0
Skin and subcutaneous tissue disorders
Alopecia † 1	17/127 (13.39%)	20/126 (15.87%)	19/126 (15.08%)	/0	/0	/0
Dry skin † 1	22/127 (17.32%)	24/126 (19.05%)	16/126 (12.70%)	/0	/0	/0
Erythema † 1	9/127 (7.09%)	7/126 (5.56%)	1/126 (0.79%)	/0	/0	/0
Palmar-plantar erythrodysaesthesia syndrome † 1	8/127 (6.30%)	1/126 (0.79%)	3/126 (2.38%)	/0	/0	/0
Pruritus † 1	20/127 (15.75%)	13/126 (10.32%)	29/126 (23.02%)	/0	/0	/0
Rash † 1	39/127 (30.71%)	39/126 (30.95%)	51/126 (40.48%)	/0	/0	/0
Rash maculo-papular † 1	16/127 (12.60%)	20/126 (15.87%)	9/126 (7.14%)	/0	/0	/0
Vascular disorders
Hypertension † 1	9/127 (7.09%)	11/126 (8.73%)	8/126 (6.35%)	/0	/0	/0
1 Term from vocabulary, MedDRA (25.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Study director
• Organization: Novartis Pharmaceuticals
• Phone: 862-778-8300
• EMail: novartis.email@novartis.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rugo HS, Lerebours F, Ciruelos E, Drullinsky P, Ruiz-Borrego M, Neven P, Park YH, Prat A, Bachelot T, Juric D, Turner N, Sophos N, Zarate JP, Arce C, Shen YM, Turner S, Kanakamedala H, Hsu WC, Chia S. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study. Lancet Oncol. 2021 Apr;22(4):489-498. doi: 10.1016/S1470-2045(21)00034-6. Erratum In: Lancet Oncol. 2021 May;22(5):e184.

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT03056755
• Other Study ID Numbers: CBYL719X2402; 2016-004586-67 ( EudraCT Number )
• First Submitted: February 15, 2017
• First Posted: February 17, 2017
• Results First Submitted: February 29, 2024
• Results First Posted: March 27, 2024
• Last Update Posted: March 27, 2024