Abstract P1-18-03: Alpelisib + fulvestrant in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC) previously treated with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + aromatase inhibitor (AI): 18-month follow-up of BYLieve Cohort A
Authors: Ciruelos Eva M , Lerebours Florence , Rugo Hope S , Ruiz-Borrego Manuel , Drullinsky Pamela , Prat Aleix , Bachelot Thomas , Neven Patrick , Park Yeon Hee , Turner Nicholas , Juric Dejan , Gu Ennan , Arce Christina H , Akdere Murat , Chia Stephen 
Published: March 2022

Abstract
Introduction: In HR+, HER2- ABC, activating PIK3CA mutations occur in ~40% of tumors and confer worse prognosis, including endocrine therapy (ET) resistance. BYLieve (NCT03056755) is an ongoing Phase II, open-label, 3-cohort noncomparative study, evaluating the PI3Kα inhibitor and degrader alpelisib (ALP) + ET (fulvestrant [FUL] or letrozole) in patients (pts) with PIK3CA-mutated, HR+, HER2- ABC progressing on/after prior treatment, including CDK4/6i + ET. This study is of high clinical relevance as ET + CDK4/6i is the recommended standard of care for first-line treatment of pts with HR+, HER2- ABC. In Cohort A, pts received CDK4/6i + AI as immediate prior therapy and received ALP + FUL as study treatment. In the primary analysis, the primary endpoint was met with 50.4% (95% confidence interval [CI], 41.2%-59.6%) of the 121 pts in the Cohort A modified full analysis set (mFAS) alive and without disease progression at 6 mo. Median progression-free survival (mPFS) and overall survival (mOS) were 7.3 mo (95% CI, 5.6-8.3) and 17.3 mo (95% CI, 17.2-20.7), respectively. The most frequent grade ≥3 adverse events (AEs) in the 127 pts in the Cohort A safety set were hyperglycemia (28%), rash (9%), and rash maculopapular (9%). This analysis focuses on updated efficacy and safety endpoints reflective of all pts achieving ~18-mo follow-up. Methods: Pts in Cohort A received ≥1 dose of ALP 300 mg orally QD + FUL 500 mg intramuscular Q28D + C1D15. For the 18-mo follow-up, efficacy endpoints, including PFS, OS, overall response rate (ORR), clinical benefit rate (CBR), duration of response (DOR) in pts with complete or partial response, and PFS on next line of treatment (PFS2), will be analyzed on the mFAS, which includes pts with a centrally confirmed PIK3CA mutation in tumor tissue. Safety of ALP + FUL, including AEs and laboratory toxicities, will be evaluated in the safety set, which includes all pts who received ≥1 dose of study treatment. Results: Of the 127 pts enrolled in Cohort A and part of the safety set, 121 were included in the mFAS. We will present efficacy endpoint results from the pts in Cohort A along with the long-term safety profile of the ALP + FUL combination. Conclusion: These data will provide insights on the long-term efficacy and safety of ALP + FUL. This combination is currently approved and used, in the clinical setting, for the treatment of pts with HR+, HER2- PIK3CA-mutated ABC.
Citation Format: Eva M Ciruelos, Florence Lerebours, Hope S Rugo, Manuel Ruiz-Borrego, Pamela Drullinsky, Aleix Prat, Thomas Bachelot, Patrick Neven, Yeon Hee Park, Nicholas Turner, Dejan Juric, Ennan Gu, Christina H Arce, Murat Akdere, Stephen Chia. Alpelisib + fulvestrant in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC) previously treated with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + aromatase inhibitor (AI): 18-month follow-up of BYLieve Cohort A [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-03.