Effectiveness of Alpelisib + Fulvestrant Compared with Real-World Standard Treatment Among Patients with HR+, HER2–, PIK3CA-Mutated Breast Cancer

• DOI: 10.1002/onco.13804
• Publication Date: 2021-04-28T19:17:38Z
• Authors: Stuart Turner; Stephen Chia; Hemanth Kanakamedala; Wei-Chun Hsu; Jinhee Park; David Chandiwana; Antonia Ridolfi; Chu-Ling Yu; Juan Pablo Zarate; Hope S. Rugo
• Keywords: Fulvestrant; Aromatase inhibitor; Letrozole; Palbociclib

Abstract Background The BYLieve trial (NCT03056755) confirmed efficacy and safety of alpelisib with fulvestrant for hormone receptor–positive (HR+), human epidermal growth factor receptor-2–negative (HER2−), PIK3CA-mutated advanced breast cancer (ABC), after cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) an aromatase (AI) as immediate prior therapy. Further analyses were performed to compare from effectiveness standard treatment in the real-world setting. Materials Methods Patients who progressed on a CDK4/6i plus AI treated matched patient cohort received standard-of-care deidentified clinico-genomics database (CGDB). Primary secondary endpoints progression-free survival (PFS), estimated by Kaplan-Meier method, proportion patients remaining at 6 months, respectively, between two cohorts. Results A total 855 PIK3CA-mutant disease had therapy selected CGDB; further matching 120 95 without exposure HER2-targeting agents, clinical study drug, or alpelisib. In unadjusted postmatching results, primary favored more than treatments cohort. Postadjustment, median PFS was 7.3 versus 3.7 months cohort, 6-month 54.6% 40.1%, respectively. Conclusion Matched/weighted analysis comparing setting supports benefit HR+, HER2−, ABC treatment. Implications Practice Approximately 40% (HER2−) (ABC) have tumors, which been associated endocrine resistance. Alpelisib, α-selective phosphatidylinositol-3-kinase inhibitor, demonstrated significantly improved SOLAR-1 when combined fulvestrant. Data are limited Using data, this is first post-CDK4/6i