Phase 2
Completed N=340
Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women
Source: ClinicalTrials.gov NCT01923168 ↗Enrolled (actual)
340
Serious AEs
14.6%
Results posted
Sep 2018
Primary outcomePrimary: Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Mutant Cohort — 1.7; 3.0 Percentage of Participants — p=0.282
Summary
The purpose of the study was to determine whether treatment with a PI3K inhibitor plus letrozole led to an increase in pathologic clinical response and Objective Response Rate compared to treatment with placebo plus letrozole in patients with Breast cancer.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Mutant Cohort |
1.7; 3.0 | 0.282 |
| PRIMARY Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Wild-type Cohort |
2.8; 1.7 | 0.697 |
| PRIMARY Objective Response Rate Per Investigator Assessment According to RECIST 1.1 for Alpelisib vs. Placebo - PIK3CA Mutant Cohort |
43.3; 44.8 | 0.435 |
| PRIMARY Objective Response Rate According to RECIST 1.1 Per Investigator Assessment for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort |
63.4; 61.0 | 0.611 |
| SECONDARY 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 |
— | — |
| SECONDARY 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 |
— | — |
| SECONDARY Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Mutant Cohort |
56.7; 50.7; 15.0; 9.0 | — |
| SECONDARY Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort |
50.7; 62.7; 18.3; 8.5 | — |
| SECONDARY Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Responders as Per pCR |
5.0; 11.0; -80.0; 80.0 | — |
| SECONDARY Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Non-responders as Per pCR |
14.0; 13.0; -62.5; -60.0; -51.2; -60.0 | — |
| SECONDARY Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort: Responders as Per pCR |
16.5; 20.0; -80.0; -45.0 | — |
| SECONDARY Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort: Non-responders as Per pCR |
16.0; 18.0; -60.0; -52.0; -60.0; -71.1 | — |
| SECONDARY Preoperative Endocrine Prognostic Index (PEPI) Response as Per Central Assessment for Alpelisib vs. Placebo - PIK3CA Mutant Cohort |
1; 0 | — |
| SECONDARY Preoperative Endocrine Prognostic Index (PEPI) Response as Per Central Assessment for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort |
1; 1 | — |
| SECONDARY Alpelisib PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1 |
30800; 27300 | — |
| SECONDARY Alpelisib PK Parameter: Cmax at Cycle 1 Day 1 |
3160 | — |
| SECONDARY Alpelisib and PK Parameter: Tmax at Cycle 1 Day 1 |
2.93 | — |
| SECONDARY Alpelisib PK Parameters: AUC0-24, AUClast at Cycle 4 Day 1 |
38000; 38000 | — |
| SECONDARY Alpelisib PK Parameter: Cmax at Cycle 4 Day 1 |
3260 | — |
| SECONDARY Alpelisib PK Parameter: Tmax at Cycle 4 Day 1 |
2.99 | — |
| SECONDARY Letrozole and PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1 |
433; 427; 314; 347 | — |
| SECONDARY Letrozole PK Parameter: Cmax at Cycle 1 Day 1 |
30.2; 28 | — |
| SECONDARY Letrozole PK Parameter: Tmax at Cycle 1 Day 1 |
1.03; 2.25 | — |
| SECONDARY Letrozole PK Parameters: AUC0-24, AUClast at Cycle 4 Day 1 |
1280; 1810; 1280; 1440 | — |
| SECONDARY Letrozole PK Parameter: Cmax at Cycle 4 Day 1 |
75.6; 103 | — |
| SECONDARY Letrozole PK Parameter: Tmax at Cycle 4 Day 1 |
2; 1.17 | — |
| SECONDARY Buparlisib PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1 |
6420; 4820 | — |
| SECONDARY Buparlisib PK Parameter: Cmax at Cycle 1 Day 1 |
760 | — |
| SECONDARY Buparlisib PK Parameter: Tmax at Cycle 1 Day 1 |
1.03 | — |
| SECONDARY Buparlisib PK Parameter: AUClast at Cycle 4 Day 1 |
10400 | — |
| SECONDARY Buparlisb PK Parameter: Cmax at Cycle 4 Day 1 |
610 | — |
| SECONDARY Buparlisib PK Parameter: Tmax at Cycle 4 Day 1 |
3 | — |
Eligibility Criteria
Inclusion Criteria
- Patient is an adult, female ≥ 18 years old at the time of informed consent
- Patient has a histologically and/or cytologically confirmed diagnosis of breast cancer
- Patient is postmenopausal.
- Patient has T1c-T3, any N, M0, operable breast cancer
- Patients must have measurable disease
- Patient has diagnostic biopsy available for the analysis of PIK3CA mutation and Ki67 level.
- Patient has estrogen-receptor and/or progesterone positive breast cancer as per local laboratory testing
- Patient has HER2 negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0 or 1+ as per local laboratory testing
Exclusion Criteria
- Patient has locally recurrent or metastatic disease
- Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy) or radiotherapy for current breast cancer disease before randomization.
- Patient with type 1 diabetes mellitus or not adequately controlled type 2 diabetes mellitus
- History of acute pancreatitis within 1 year of study entry
- Uncontrolled hypertension
Data sourced from ClinicalTrials.gov (NCT01923168). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.