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Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women

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ClinicalTrials.gov Identifier: NCT01923168
Recruitment Status : Completed
First Posted : August 15, 2013
Results First Posted : September 14, 2018
Last Update Posted : September 14, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: alpelisib
Drug: buparlisib
Drug: Placebo
Enrollment 340
Recruitment Details A total of approximately 320 patients were planned to be randomized: this was based on 60 patients per arm in each cohort (PIK3CA mutant and PIK3CA wild-type) for the alpelisib+letrozole and placebo+letrozole arms, plus the estimated number of patients randomized to buparlisib+letrozole arm at the time this arm was discontinued.
Pre-assignment Details  
Arm/Group Title Alpelisib + Letrozole Buparlisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily. Participants took buparlisib 100 mg once daily or 5 days on/2 days off plus letrozole 2.5 mg once daily. Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Period Title: Overall Study
Started 131 83 126
Completed 94 44 109
Not Completed 37 39 17
Reason Not Completed
Protocol Violation             1             1             0
Subject/guardian decision             14             14             4
Adverse Event             12             12             0
Physician Decision             6             9             5
Progressive disease             4             3             7
Death             0             0             1
Arm/Group Title Alpelisib + Letrozole Buparlisib + Letrozole Placebo + Letrozole Total
Hide Arm/Group Description Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily. Participants took buparlisib 100 mg once daily or 5 days on/2 days off plus letrozole 2.5 mg once daily. Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily. Total of all reporting groups
Overall Number of Baseline Participants 131 83 126 340
Hide Baseline Analysis Population Description
The Full Analysis Set (FAS) comprised all randomized subjects in the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 131 participants 83 participants 126 participants 340 participants
64.3  (8.53) 65.2  (8.61) 63.1  (8.31) 64.1  (8.49)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 131 participants 83 participants 126 participants 340 participants
Female
131
 100.0%
83
 100.0%
126
 100.0%
340
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 131 participants 83 participants 126 participants 340 participants
White
117
  89.3%
68
  81.9%
105
  83.3%
290
  85.3%
Asian
7
   5.3%
4
   4.8%
10
   7.9%
21
   6.2%
Black or African American
3
   2.3%
3
   3.6%
5
   4.0%
11
   3.2%
Other
3
   2.3%
6
   7.2%
3
   2.4%
12
   3.5%
Unknown
1
   0.8%
2
   2.4%
3
   2.4%
6
   1.8%
1.Primary Outcome
Title Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Mutant Cohort
Hide Description Pathologic complete response (pCR) defined as absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of 24 weeks of treatment by local assessment (ypT0/Tis ypN0). Patients who experienced progression of disease while undergoing neoadjuvant therapy, or who did not receive surgery for any reason, or received antineoplastic treatment other than study drug(s) before surgery were considered as non-responders for the calculation of pCR rate.
Time Frame After 24 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) for the PIK3CA mutant cohort comprised all randomized participants who were assigned to the PIK3CA mutant cohort based on tumor tissue for the randomization.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 60 67
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of Participants
1.7
(0.2 to 6.3)
3.0
(0.8 to 7.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alpelisib + Letrozole, Placebo + Letrozole
Comments [Not Specified]
Type of Statistical Test Other
Comments Bayesian double criteria
Statistical Test of Hypothesis P-Value 0.282
Comments [Not Specified]
Method Posterior mean diff. & credible interval
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.3
Confidence Interval (2-Sided) 80%
-4.5 to 1.7
Estimation Comments [Not Specified]
2.Primary Outcome
Title Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Wild-type Cohort
Hide Description Pathologic complete response (pCR) defined as absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of 24 weeks of treatment by local assessment (ypT0/Tis ypN0). Patients who experienced progression of disease while undergoing neoadjuvant therapy, or who did not receive surgery for any reason, or received antineoplastic treatment other than study drug(s) before surgery were considered as non-responders for the calculation of pCR rate.
Time Frame After 24 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) for the PIK3CA wild-type cohort comprised all randomized participants who were assigned to the PIK3CA wild-type cohort based on tumor tissue for the randomization.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 71 59
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of Participants
2.8
(0.8 to 7.3)
1.7
(0.2 to 6.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alpelisib + Letrozole, Placebo + Letrozole
Comments [Not Specified]
Type of Statistical Test Other
Comments Bayesian double criteria
Statistical Test of Hypothesis P-Value 0.697
Comments [Not Specified]
Method Posterior mean difference
Comments Posterior mean difference
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.1
Confidence Interval (2-Sided) 80%
-1.9 to 4.2
Estimation Comments [Not Specified]
3.Primary Outcome
Title Objective Response Rate Per Investigator Assessment According to RECIST 1.1 for Alpelisib vs. Placebo - PIK3CA Mutant Cohort
Hide Description

Objective Response Rate (ORR) defined as the proportion of patients with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) based on local investigator's assessment according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1.

BOR was assessed per MRI or Ultrasound and defined as per RECIST 1.1 as CR for a disappearance of all non-nodal target lesions (TL)/non-target lesions (NTL) and a reduction in short axis to < 10 mm of any pathological lymph nodes assigned as TL/NTL and no new lesion; as PR if not qualifying for CR but with a decrease from baseline ≥ 30% in the sum of diameter of all TL, no progression of NTL and no new lesion.

Time Frame After 24 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) for the PIK3CA mutant cohort comprised all randomized participants who were assigned to the PIK3CA mutant cohort based on tumor tissue for the randomization.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 60 67
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of Participants
43.3
(34.6 to 52.4)
44.8
(36.5 to 53.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alpelisib + Letrozole, Placebo + Letrozole
Comments [Not Specified]
Type of Statistical Test Other
Comments Bayesian double criteria
Statistical Test of Hypothesis P-Value 0.435
Comments [Not Specified]
Method Posterior mean diff. & credible interval
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.4
Confidence Interval (2-Sided) 80%
-12.5 to 9.7
Estimation Comments [Not Specified]
4.Primary Outcome
Title Objective Response Rate According to RECIST 1.1 Per Investigator Assessment for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort
Hide Description

Objective Response Rate (ORR) defined as the proportion of patients with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) based on local investigator's assessment according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1.

BOR was assessed per MRI or Ultrasound and defined as per RECIST 1.1 as CR for a disappearance of all non-nodal target lesions (TL)/non-target lesions (NTL) and a reduction in short axis to < 10 mm of any pathological lymph nodes assigned as TL/NTL and no new lesion; as PR if not qualifying for CR but with a decrease from baseline ≥ 30% in the sum of diameter of all TL, no progression of NTL and no new lesion.

Time Frame After 24 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) for the PIK3CA wild-type cohort comprised all randomized participants who were assigned to the PIK3CA wild-type cohort based on tumor tissue for the randomization.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 71 59
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of Participants
63.4
(55.1 to 71.0)
61.0
(51.8 to 69.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alpelisib + Letrozole, Placebo + Letrozole
Comments [Not Specified]
Type of Statistical Test Other
Comments Bayesian double criteria
Statistical Test of Hypothesis P-Value 0.611
Comments [Not Specified]
Method Posterior mean diff. & credible interval
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.4
Confidence Interval (2-Sided) 80%
-8.4 to 13.2
Estimation Comments [Not Specified]
5.Secondary Outcome
Title pCR and Objective Response Rate According to RECIST 1.1 Criteria Per Investigator Assessment for Alpelisib vs. Placebo in PIK3CA Mutant Cohort Based on ctDNA
Hide Description pCR and Objective response rate according to RECIST 1.1 per investigator assessment after 24 weeks of treatment
Time Frame After 24 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS comprised all randomized participants. This analysis was to be done in patients with PIK3CA mutation based on Circulating tumor DNA (ctDNA). Data could not be reported as the ctDNA analysis was not done after the primary endpoint was negative.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title pCR and Objective Response Rate According to RECIST 1.1 Criteria Per Investigator Assessment for Alpelisib vs. Placebo in PIK3CA Wild-type Cohort Based on ctDNA
Hide Description pCR and Objective response rate according to RECIST 1.1 per investigator assessment after 24 weeks of treatment
Time Frame After 24 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) comprised all randomized participants in the study. This analysis was to be done in PIK3CA wild-type patients based on Circulating tumor DNA (ctDNA). Data could not be reported in this table as the ctDNA analysis was not done after the primary endpoint was negative.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Mutant Cohort
Hide Description Breast conserving surgery is defined for participants who underwent surgery and did not have a mastectomy. The row "no surgery" provides the number of patients who did not undergo surgery at all for various reasons.
Time Frame After 24 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) for the PIK3CA mutant cohort comprised all randomized participants who were assigned to the PIK3CA mutant cohort based on tumor tissue for the randomization. PIK3CA mutation is based on tumor tissue.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 60 67
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of participants
Breast conserving surgery
56.7
(47.6 to 65.4)
50.7
(42.2 to 59.2)
No Surgery
15.0
(9.3 to 22.6)
9.0
(4.8 to 15.2)
8.Secondary Outcome
Title Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort
Hide Description Breast conserving surgery is defined as the percentage of participants with no mastectomy following completion of 24 weeks of treatment. Breast conserving surgery is defined for participants who underwent surgery and did not have a mastectomy. The row "no surgery" provides the number of patients who did not undergo surgery at all for various reasons.
Time Frame After 24 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) for the PIK3CA wild-type cohort comprised all randomized participants who were assigned to the PIK3CA wild-type cohort based on tumor tissue for the randomization. PIK3CA mutation is based on tumor tissue.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 71 59
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of participants
Breast conserving surgery
50.7
(42.5 to 58.9)
62.7
(53.6 to 71.2)
No Surgery
18.3
(12.5 to 25.6)
8.5
(4.5 to 15.2)
9.Secondary Outcome
Title Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Responders as Per pCR
Hide Description Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Responders as Per pCR
Time Frame Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS for the PIK3CA mutant cohort comprised all randomized participants who were assigned to the PIK3CA mutant cohort based on tumor tissue for the randomization. Only responders as per pCR were considered for this analysis. No patient had data reported at end of trial (EOT), hence the percent change from baseline at EOT could not be reported.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 1 2
Median (Full Range)
Unit of Measure: Percentage of positive cells
Baseline Number Analyzed 1 participants 2 participants
5.0
(5 to 5)
11.0
(5 to 17)
C1D15: % change from Baseline Number Analyzed 1 participants 1 participants
-80.0
(-80 to -80)
80.0
(80 to 80)
EOT % change from Baseline Number Analyzed 0 participants 0 participants
10.Secondary Outcome
Title Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Non-responders as Per pCR
Hide Description Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Non-responders as Per pCR.
Time Frame Baseline, Cycle 1 Day 15 (each cycle is 28 days ) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) for the PIK3CA mutant cohort comprised all randomized participants who were assigned to the PIK3CA mutant cohort based on tumor tissue for the randomization. Only non-responders as per pCR are considered for this analysis.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 59 65
Median (Full Range)
Unit of Measure: Percentage of positive cells
Baseline Number Analyzed 59 participants 65 participants
14.0
(0 to 82)
13.0
(3 to 89)
C1D15 % change from Baseline Number Analyzed 45 participants 52 participants
-62.5
(-97 to 467)
-60.0
(-96 to 733)
EOT % change from Baseline Number Analyzed 34 participants 49 participants
-51.2
(-94 to 400)
-60.0
(-97 to 223)
11.Secondary Outcome
Title Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort: Responders as Per pCR
Hide Description Association between pCR and changes in Ki67 from baseline for alpelisib vs. placebo - PIK3CA wild-type cohort: responders as per pCR
Time Frame Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS for PIK3CA wild-type cohort comprised all rand. Parts. assigned to PIK3CA wild-type cohort based on tumor tissue for rand. Only responders as per pCR were considered for this analysis. No patient had data reported at C1D15 & EOT for Placebo, hence percent change from baseline could not be reported.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 2 1
Median (Full Range)
Unit of Measure: Percentage of positive cells
Baseline Number Analyzed 2 participants 1 participants
16.5
(3 to 30)
20.0
(20 to 20)
C1D15: % change from Baseline Number Analyzed 1 participants 0 participants
-80.0
(-80 to -80)
EOT % change from Baseline Number Analyzed 2 participants 0 participants
-45.0
(-90 to 0)
12.Secondary Outcome
Title Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort: Non-responders as Per pCR
Hide Description Association between pCR and changes in Ki67 from baseline for alpelisib vs. placebo - PIK3CA wild-type cohort: non-responders as per pCR
Time Frame Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) for the PIK3CA wild-type cohort comprised all randomized participants who were assigned to the PIK3CA wild-type cohort based on tumor tissue for the randomization. Only non-responders as per pCR are considered for this analysis.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 69 58
Median (Full Range)
Unit of Measure: Percentage of positive cells
Baseline Number Analyzed 69 participants 58 participants
16.0
(3 to 60)
18.0
(4 to 85)
C1D15 % change from Baseline Number Analyzed 51 participants 47 participants
-60.0
(-97 to 220)
-52.0
(-93 to 50)
EOT % change from Baseline Number Analyzed 37 participants 41 participants
-60.0
(-90 to 190)
-71.1
(-100 to 250)
13.Secondary Outcome
Title Preoperative Endocrine Prognostic Index (PEPI) Response as Per Central Assessment for Alpelisib vs. Placebo - PIK3CA Mutant Cohort
Hide Description Preoperative endocrine prognostic index (PEPI) response as per central assessment for alpelisib vs. placebo - PIK3CA mutant cohort. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and ER status of the surgical specimen (Ellis et al, Contemp Clin Trials 2008). The PEPI score ranges from 0 to to 12, and a higher score means a worse outcome. PEPI response is defined as a PEPI score of 0.
Time Frame At the time of surgery (expected after 24 weeks of treatment)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) for the PIK3CA mutant cohort comprised all randomized participants who were assigned to the PIK3CA mutant cohort based on tumor tissue for the randomization.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 60 67
Measure Type: Number
Unit of Measure: Number of participants
1 0
14.Secondary Outcome
Title Preoperative Endocrine Prognostic Index (PEPI) Response as Per Central Assessment for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort
Hide Description Preoperative endocrine prognostic index (PEPI) response as per central assessment for alpelisib vs. placebo - PIK3CA wild-type cohort. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and ER status of the surgical specimen (Ellis et al, Contemp Clin Trials 2008). The PEPI score ranges from 0 to to 12, and a higher score means a worse outcome. PEPI response is defined as a PEPI score of 0.
Time Frame At the time of surgery (expected after 24 weeks of treatment)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) for the PIK3CA wild-type cohort comprised all randomized participants who were assigned to the PIK3CA wild-type cohort based on tumor tissue for the randomization.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 71 59
Measure Type: Number
Unit of Measure: Number of participants
1 1
15.Secondary Outcome
Title Alpelisib PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1
Hide Description Summary of primary PK parameters for alpelisib plasma concentration
Time Frame 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The BYL FPAS included participants who received at least 1 dose of alpelisib, had at least 1 evaluable post-treatment alpelisib concentration, received adequate doses of alpelisib and letrozole prior to full PK assessment, did not vomit within 4 hours of alpelisib or letrozole dosing on the day of full PK and had an evaluable full PK profile.
Arm/Group Title Alpelisib + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
AUC0-24 Number Analyzed 3 participants
30800
(20.6%)
AUClast Number Analyzed 5 participants
27300
(68.6%)
16.Secondary Outcome
Title Alpelisib PK Parameter: Cmax at Cycle 1 Day 1
Hide Description Summary of primary PK parameters for alpelisib plasma concentration
Time Frame Cycle 1 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The BYL FPAS included participants who received at least 1 dose of alpelisib, had at least 1 evaluable post-treatment alpelisib concentration, received adequate doses of alpelisib and letrozole prior to full PK assessment, did not vomit within 4 hours of alpelisib or letrozole dosing on the day of full PK and had an evaluable full PK profile.
Arm/Group Title Alpelisib + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
3160
(25.3%)
17.Secondary Outcome
Title Alpelisib and PK Parameter: Tmax at Cycle 1 Day 1
Hide Description Summary of primary PK parameters for alpelisib plasma concentration
Time Frame Cycle 1 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Alpelisib Pharmacokinetic Analysis Set (BYL PAS): The BYL PAS included all participants who received at least one dose of alpelisib and had at least one evaluable post-treatment alpelisib concentration measurement.
Arm/Group Title Alpelisib + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 5
Median (Full Range)
Unit of Measure: HR
2.93
(1 to 6)
18.Secondary Outcome
Title Alpelisib PK Parameters: AUC0-24, AUClast at Cycle 4 Day 1
Hide Description Summary of primary PK parameters for alpelisib plasma concentration
Time Frame 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The BYL FPAS included participants who received at least 1 dose of alpelisib, had at least 1 evaluable post-treatment alpelisib concentration, received adequate doses of alpelisib and letrozole prior to full PK assessment, did not vomit within 4 hours of alpelisib or letrozole dosing on the day of full PK and had an evaluable full PK profile.
Arm/Group Title Alpelisib + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
AUC0-24 Number Analyzed 2 participants
38000
(13.2%)
AUClast Number Analyzed 2 participants
38000
(13.1%)
19.Secondary Outcome
Title Alpelisib PK Parameter: Cmax at Cycle 4 Day 1
Hide Description Summary of primary PK parameters for alpelisib plasma concentration
Time Frame Cycle 4 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Alpelisib Pharmacokinetic Analysis Set (BYL PAS): The BYL PAS included all participants who received at least one dose of alpelisib and had at least one evaluable post-treatment alpelisib concentration measurement.
Arm/Group Title Alpelisib + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
3260
(26.7%)
20.Secondary Outcome
Title Alpelisib PK Parameter: Tmax at Cycle 4 Day 1
Hide Description Summary of primary PK parameters for alpelisib plasma concentration
Time Frame Cycle 4 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Alpelisib Pharmacokinetic Analysis Set (BYL PAS): The BYL PAS included all participants who received at least one dose of alpelisib and had at least one evaluable post-treatment alpelisib concentration measurement.
Arm/Group Title Alpelisib + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 5
Median (Full Range)
Unit of Measure: hr
2.99
(2.98 to 3)
21.Secondary Outcome
Title Letrozole and PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1
Hide Description Summary of primary PK parameters for Letrozole plasma concentration
Time Frame 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The LZ FPAS included participants who received at least 1 dose of letrozole, had at least 1 evaluable post-treatment letrozole concentration, received adequate doses of letrozole prior to full PK assessment, did not vomit within 4 hours of letrozole dosing on the day of full PK and had an evaluable full PK profile.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 5 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
AUC0-24 Number Analyzed 3 participants 10 participants
433
(36.3%)
427
(28.8%)
AUClast Number Analyzed 5 participants 14 participants
314
(96.9%)
347
(49.6%)
22.Secondary Outcome
Title Letrozole PK Parameter: Cmax at Cycle 1 Day 1
Hide Description Summary of primary PK parameters for letrozole plasma concentration
Time Frame Cycle 1 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The LZ FPAS included participants who received at least 1 dose of letrozole, had at least 1 evaluable post-treatment letrozole concentration, received adequate doses of letrozole prior to full PK assessment, did not vomit within 4 hours of letrozole dosing on the day of full PK and had an evaluable full PK profile.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 5 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
30.2
(33.2%)
28
(42.3%)
23.Secondary Outcome
Title Letrozole PK Parameter: Tmax at Cycle 1 Day 1
Hide Description Summary of primary PK parameters for letrozole plasma concentration
Time Frame Cycle 1 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The LZ FPAS included participants who received at least 1 dose of letrozole, had at least 1 evaluable post-treatment letrozole concentration, received adequate doses of letrozole prior to full PK assessment, did not vomit within 4 hours of letrozole dosing on the day of full PK and had an evaluable full PK profile.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 5 15
Median (Full Range)
Unit of Measure: hr
1.03
(1 to 3)
2.25
(1 to 24.5)
24.Secondary Outcome
Title Letrozole PK Parameters: AUC0-24, AUClast at Cycle 4 Day 1
Hide Description Summary of primary PK parameters for Letrozole plasma concentration
Time Frame 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Letrozole Pharmacokinetic Analysis Set (LZ PAS): The LZ PAS included all participants who received at least one dose of letrozole and had at least one evaluable post-treatment letrozole concentration measurement.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 5 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
AUC0-24 Number Analyzed 2 participants 8 participants
1280
(18%)
1810
(33.1%)
AUClast Number Analyzed 2 participants 13 participants
1280
(17.9%)
1440
(66.7%)
25.Secondary Outcome
Title Letrozole PK Parameter: Cmax at Cycle 4 Day 1
Hide Description Summary of primary PK parameters for letrozole plasma concentration
Time Frame Cycle 4 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The LZ FPAS included participants who received at least 1 dose of letrozole, had at least 1 evaluable post-treatment letrozole concentration, received adequate doses of letrozole prior to full PK assessment, did not vomit within 4 hours of letrozole dosing on the day of full PK and had an evaluable full PK profile.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 5 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
75.6
(6.84%)
103
(30%)
26.Secondary Outcome
Title Letrozole PK Parameter: Tmax at Cycle 4 Day 1
Hide Description Summary of primary PK parameters for letrozole plasma concentration
Time Frame Cycle 4 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The LZ FPAS included participants who received at least 1 dose of letrozole, had at least 1 evaluable post-treatment letrozole concentration, received adequate doses of letrozole prior to full PK assessment, did not vomit within 4 hours of letrozole dosing on the day of full PK and had an evaluable full PK profile.
Arm/Group Title Alpelisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description:
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.
Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 5 15
Median (Full Range)
Unit of Measure: hr
2
(1 to 3)
1.17
(1 to 6)
27.Secondary Outcome
Title Buparlisib PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1
Hide Description Summary of primary PK parameters for Buparlisib plasma concentration
Time Frame 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The BKM FPAS included participants who received at least 1 dose of buparlisib, had at least 1 evaluable post-treatment concentration, received adequate doses of buparlisib and letrozole prior to full PK assessment, did not vomit within 4 hours of buparlisib or letrozole dosing on the day of full PK and had an evaluable full PK profile.
Arm/Group Title Buparlisib + Letrozole
Hide Arm/Group Description:
Participants took buparlisib 100 mg once daily or 5 days on/2 days off plus letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
AUC0-24 Number Analyzed 8 participants
6420
(60%)
AUClast Number Analyzed 9 participants
4820
(123%)
28.Secondary Outcome
Title Buparlisib PK Parameter: Cmax at Cycle 1 Day 1
Hide Description Summary of primary PK parameters for buparlisib plasma concentration
Time Frame Cycle 1 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The BKM FPAS included participants who received at least 1 dose of buparlisib, had at least 1 evaluable post-treatment concentration, received adequate doses of buparlisib and letrozole prior to full PK assessment, did not vomit within 4 hours of buparlisib or letrozole dosing on the day of full PK and had an evaluable full PK profile.
Arm/Group Title Buparlisib + Letrozole
Hide Arm/Group Description:
Participants took buparlisib 100 mg once daily or 5 days on/2 days off plus letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
760
(86.7%)
29.Secondary Outcome
Title Buparlisib PK Parameter: Tmax at Cycle 1 Day 1
Hide Description Summary of primary PK parameters for buparlisib plasma concentration
Time Frame Cycle 1 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Buparlisib Pharmacokinetic Analysis Set (BKM PAS): The BKM PAS included all participants who received at least one dose of buparlisib and had at least one evaluable post-treatment buparlisib concentration measurement.
Arm/Group Title Buparlisib + Letrozole
Hide Arm/Group Description:
Participants took buparlisib 100 mg once daily or 5 days on/2 days off plus letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 10
Median (Full Range)
Unit of Measure: hr
1.03
(0.5 to 3.5)
30.Secondary Outcome
Title Buparlisib PK Parameter: AUClast at Cycle 4 Day 1
Hide Description Summary of primary PK parameters for Buparlisib plasma concentration
Time Frame 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
BKM FPAS: The BKM FPAS included participants who received at least 1 dose of buparlisib, had at least 1 evaluable post-treatment concentration, received adequate doses of buparlisib and letrozole prior to full PK assessment, did not vomit within 4 hours of buparlisib or letrozole dosing on the day of full PK and had an evaluable full PK profile.
Arm/Group Title Buparlisib + Letrozole
Hide Arm/Group Description:
Participants took buparlisib 100 mg once daily or 5 days on/2 days off plus letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 10
Median (Full Range)
Unit of Measure: ng*hr/mL
10400
(10400 to 10400)
31.Secondary Outcome
Title Buparlisb PK Parameter: Cmax at Cycle 4 Day 1
Hide Description Summary of primary PK parameters for buparlisib plasma concentration
Time Frame Cycle 4 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Buparlisib Pharmacokinetic Analysis Set (BKM PAS): The BKM PAS included all participants who received at least one dose of buparlisib and had at least one evaluable post-treatment buparlisib concentration measurement.
Arm/Group Title Buparlisib + Letrozole
Hide Arm/Group Description:
Participants took buparlisib 100 mg once daily or 5 days on/2 days off plus letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 10
Median (Full Range)
Unit of Measure: ng/mL
610
(610 to 610)
32.Secondary Outcome
Title Buparlisib PK Parameter: Tmax at Cycle 4 Day 1
Hide Description Summary of primary PK parameters for buparlisib plasma concentration
Time Frame Cycle 4 Day 1 (each cycle is 28 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Buparlisib Pharmacokinetic Analysis Set (BKM PAS): The BKM PAS included all participants who received at least one dose of buparlisib and had at least one evaluable post-treatment buparlisib concentration measurement.
Arm/Group Title Buparlisib + Letrozole
Hide Arm/Group Description:
Participants took buparlisib 100 mg once daily or 5 days on/2 days off plus letrozole 2.5 mg once daily.
Overall Number of Participants Analyzed 10
Median (Full Range)
Unit of Measure: hr
3
(3 to 3)
Time Frame All Adverse Events reported in this record are on-treatment events (from first dose of study treatment to last dose of study treatment + 30 days, duration expected to be a total of approximately 25 weeks).
Adverse Event Reporting Description Adverse Events, Serious Adverse Events based on Safety Set population defined as all patients who received at least one dose of study treatment
 
Arm/Group Title Alpelisib + Letrozole Buparlisib + Letrozole Placebo + Letrozole
Hide Arm/Group Description Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily. Participants took buparlisib 100 mg once daily or 5 days on/2 days off plus letrozole 2.5 mg once daily. Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.
All-Cause Mortality
Alpelisib + Letrozole Buparlisib + Letrozole Placebo + Letrozole
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/130 (0.77%)   0/81 (0.00%)   1/125 (0.80%) 
Show Serious Adverse Events Hide Serious Adverse Events
Alpelisib + Letrozole Buparlisib + Letrozole Placebo + Letrozole
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   21/130 (16.15%)   22/81 (27.16%)   6/125 (4.80%) 
Cardiac disorders       
Atrial fibrillation  1  0/130 (0.00%)  2/81 (2.47%)  0/125 (0.00%) 
Cardiac disorder  1  0/130 (0.00%)  1/81 (1.23%)  0/125 (0.00%) 
Cardiac failure  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
Stress cardiomyopathy  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
Eye disorders       
Iritis  1  0/130 (0.00%)  1/81 (1.23%)  0/125 (0.00%) 
Gastrointestinal disorders       
Colitis  1  1/130 (0.77%)  2/81 (2.47%)  0/125 (0.00%) 
Diarrhoea  1  1/130 (0.77%)  1/81 (1.23%)  0/125 (0.00%) 
Nausea  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
Stomatitis  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
Vomiting  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
General disorders       
Disease progression  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
General physical health deterioration  1  2/130 (1.54%)  1/81 (1.23%)  0/125 (0.00%) 
Generalised oedema  1  0/130 (0.00%)  1/81 (1.23%)  0/125 (0.00%) 
Malaise  1  0/130 (0.00%)  1/81 (1.23%)  0/125 (0.00%) 
Oedema peripheral  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
Pyrexia  1  2/130 (1.54%)  0/81 (0.00%)  0/125 (0.00%) 
Sudden death  1  0/130 (0.00%)  0/81 (0.00%)  1/125 (0.80%) 
Hepatobiliary disorders       
Hepatotoxicity  1  0/130 (0.00%)  3/81 (3.70%)  0/125 (0.00%) 
Hypertransaminasaemia  1  0/130 (0.00%)  1/81 (1.23%)  0/125 (0.00%) 
Immune system disorders       
Hypersensitivity  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
Infections and infestations       
Appendicitis  1  0/130 (0.00%)  0/81 (0.00%)  1/125 (0.80%) 
Gastroenteritis  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
Respiratory tract infection  1  1/130 (0.77%)  0/81 (0.00%)  1/125 (0.80%) 
Sepsis  1  1/130 (0.77%)  1/81 (1.23%)  0/125 (0.00%) 
Injury, poisoning and procedural complications       
Accidental overdose  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
Contusion  1  0/130 (0.00%)  0/81 (0.00%)  1/125 (0.80%) 
Post procedural haematoma  1  0/130 (0.00%)  1/81 (1.23%)  0/125 (0.00%) 
Investigations       
Alanine aminotransferase increased  1  0/130 (0.00%)  7/81 (8.64%)  0/125 (0.00%) 
Aspartate aminotransferase increased  1  0/130 (0.00%)  6/81 (7.41%)  0/125 (0.00%) 
Blood bilirubin increased  1  0/130 (0.00%)  1/81 (1.23%)  0/125 (0.00%) 
Ejection fraction decreased  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
Metabolism and nutrition disorders       
Dehydration  1  2/130 (1.54%)  0/81 (0.00%)  0/125 (0.00%) 
Hypercalcaemia  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
Hyperglycaemia  1  7/130 (5.38%)  0/81 (0.00%)  0/125 (0.00%) 
Hyperuricaemia  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
Hyponatraemia  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
Nervous system disorders       
Syncope  1  0/130 (0.00%)  1/81 (1.23%)  0/125 (0.00%) 
Transient ischaemic attack  1  0/130 (0.00%)  0/81 (0.00%)  1/125 (0.80%) 
Renal and urinary disorders       
Ureterolithiasis  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  2/130 (1.54%)  0/81 (0.00%)  0/125 (0.00%) 
Epistaxis  1  0/130 (0.00%)  1/81 (1.23%)  0/125 (0.00%) 
Hypoxia  1  0/130 (0.00%)  0/81 (0.00%)  1/125 (0.80%) 
Pleural effusion  1  2/130 (1.54%)  0/81 (0.00%)  0/125 (0.00%) 
Pulmonary embolism  1  0/130 (0.00%)  0/81 (0.00%)  1/125 (0.80%) 
Skin and subcutaneous tissue disorders       
Angioedema  1  0/130 (0.00%)  1/81 (1.23%)  0/125 (0.00%) 
Pruritus  1  2/130 (1.54%)  0/81 (0.00%)  0/125 (0.00%) 
Rash  1  3/130 (2.31%)  2/81 (2.47%)  0/125 (0.00%) 
Rash maculo-papular  1  2/130 (1.54%)  2/81 (2.47%)  0/125 (0.00%) 
Skin necrosis  1  0/130 (0.00%)  1/81 (1.23%)  0/125 (0.00%) 
Vascular disorders       
Deep vein thrombosis  1  1/130 (0.77%)  0/81 (0.00%)  0/125 (0.00%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Alpelisib + Letrozole Buparlisib + Letrozole Placebo + Letrozole
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   126/130 (96.92%)   80/81 (98.77%)   106/125 (84.80%) 
Cardiac disorders       
Tachycardia  1  3/130 (2.31%)  5/81 (6.17%)  1/125 (0.80%) 
Ear and labyrinth disorders       
Vertigo  1  5/130 (3.85%)  5/81 (6.17%)  6/125 (4.80%) 
Eye disorders       
Vision blurred  1  9/130 (6.92%)  3/81 (3.70%)  0/125 (0.00%) 
Gastrointestinal disorders       
Abdominal distension  1  3/130 (2.31%)  6/81 (7.41%)  4/125 (3.20%) 
Abdominal pain  1  7/130 (5.38%)  5/81 (6.17%)  4/125 (3.20%) 
Abdominal pain upper  1  5/130 (3.85%)  7/81 (8.64%)  4/125 (3.20%) 
Constipation  1  5/130 (3.85%)  7/81 (8.64%)  13/125 (10.40%) 
Diarrhoea  1  66/130 (50.77%)  29/81 (35.80%)  19/125 (15.20%) 
Dry mouth  1  14/130 (10.77%)  5/81 (6.17%)  4/125 (3.20%) 
Dyspepsia  1  11/130 (8.46%)  11/81 (13.58%)  6/125 (4.80%) 
Nausea  1  57/130 (43.85%)  37/81 (45.68%)  23/125 (18.40%) 
Stomatitis  1  42/130 (32.31%)  18/81 (22.22%)  5/125 (4.00%) 
Vomiting  1  23/130 (17.69%)  6/81 (7.41%)  6/125 (4.80%) 
General disorders       
Asthenia  1  21/130 (16.15%)  16/81 (19.75%)  17/125 (13.60%) 
Chills  1  7/130 (5.38%)  8/81 (9.88%)  5/125 (4.00%) 
Fatigue  1  53/130 (40.77%)  30/81 (37.04%)  42/125 (33.60%) 
Mucosal dryness  1  7/130 (5.38%)  2/81 (2.47%)  0/125 (0.00%) 
Oedema peripheral  1  9/130 (6.92%)  4/81 (4.94%)  4/125 (3.20%) 
Pyrexia  1  12/130 (9.23%)  1/81 (1.23%)  3/125 (2.40%) 
Infections and infestations       
Urinary tract infection  1  15/130 (11.54%)  7/81 (8.64%)  7/125 (5.60%) 
Viral upper respiratory tract infection  1  5/130 (3.85%)  5/81 (6.17%)  13/125 (10.40%) 
Injury, poisoning and procedural complications       
Procedural pain  1  2/130 (1.54%)  5/81 (6.17%)  9/125 (7.20%) 
Investigations       
Alanine aminotransferase increased  1  14/130 (10.77%)  49/81 (60.49%)  3/125 (2.40%) 
Aspartate aminotransferase increased  1  11/130 (8.46%)  44/81 (54.32%)  2/125 (1.60%) 
Blood bilirubin increased  1  2/130 (1.54%)  6/81 (7.41%)  1/125 (0.80%) 
Blood creatinine increased  1  12/130 (9.23%)  1/81 (1.23%)  4/125 (3.20%) 
Blood glucose increased  1  12/130 (9.23%)  3/81 (3.70%)  2/125 (1.60%) 
Gamma-glutamyltransferase increased  1  5/130 (3.85%)  6/81 (7.41%)  1/125 (0.80%) 
Weight decreased  1  16/130 (12.31%)  10/81 (12.35%)  3/125 (2.40%) 
Metabolism and nutrition disorders       
Decreased appetite  1  40/130 (30.77%)  25/81 (30.86%)  10/125 (8.00%) 
Hyperglycaemia  1  69/130 (53.08%)  38/81 (46.91%)  8/125 (6.40%) 
Hypokalaemia  1  9/130 (6.92%)  1/81 (1.23%)  0/125 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  11/130 (8.46%)  13/81 (16.05%)  34/125 (27.20%) 
Back pain  1  1/130 (0.77%)  7/81 (8.64%)  11/125 (8.80%) 
Muscle spasms  1  13/130 (10.00%)  5/81 (6.17%)  5/125 (4.00%) 
Musculoskeletal pain  1  2/130 (1.54%)  4/81 (4.94%)  7/125 (5.60%) 
Myalgia  1  6/130 (4.62%)  4/81 (4.94%)  13/125 (10.40%) 
Nervous system disorders       
Dizziness  1  7/130 (5.38%)  22/81 (27.16%)  19/125 (15.20%) 
Dysgeusia  1  24/130 (18.46%)  11/81 (13.58%)  7/125 (5.60%) 
Headache  1  26/130 (20.00%)  10/81 (12.35%)  16/125 (12.80%) 
Memory impairment  1  2/130 (1.54%)  5/81 (6.17%)  2/125 (1.60%) 
Paraesthesia  1  8/130 (6.15%)  2/81 (2.47%)  4/125 (3.20%) 
Tremor  1  0/130 (0.00%)  8/81 (9.88%)  1/125 (0.80%) 
Psychiatric disorders       
Anxiety  1  10/130 (7.69%)  16/81 (19.75%)  10/125 (8.00%) 
Depression  1  5/130 (3.85%)  12/81 (14.81%)  3/125 (2.40%) 
Insomnia  1  15/130 (11.54%)  8/81 (9.88%)  17/125 (13.60%) 
Reproductive system and breast disorders       
Breast pain  1  4/130 (3.08%)  8/81 (9.88%)  10/125 (8.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  9/130 (6.92%)  8/81 (9.88%)  9/125 (7.20%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  28/130 (21.54%)  3/81 (3.70%)  7/125 (5.60%) 
Dry skin  1  19/130 (14.62%)  14/81 (17.28%)  4/125 (3.20%) 
Pruritus  1  22/130 (16.92%)  18/81 (22.22%)  9/125 (7.20%) 
Rash  1  58/130 (44.62%)  31/81 (38.27%)  10/125 (8.00%) 
Rash maculo-papular  1  22/130 (16.92%)  9/81 (11.11%)  3/125 (2.40%) 
Vascular disorders       
Hot flush  1  8/130 (6.15%)  12/81 (14.81%)  31/125 (24.80%) 
Hypertension  1  16/130 (12.31%)  10/81 (12.35%)  8/125 (6.40%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01923168     History of Changes
Other Study ID Numbers: CBYL719A2201
2013-001862-41 ( EudraCT Number )
First Submitted: August 13, 2013
First Posted: August 15, 2013
Results First Submitted: July 4, 2018
Results First Posted: September 14, 2018
Last Update Posted: September 14, 2018