Effectiveness of Alpelisib + Fulvestrant Compared With Real-World Standard Treatment Among Patients With HR+, HER2–, PIK3CA-Mutated Breast Cancer
Mené sur 120 patientes atteintes d'un cancer du sein HR+ HER2- et présentant une mutation du gène PIK3CA, et à partir de données d'une cohorte incluant 855 patientes, cet essai compare l'efficacité, du point de vue de la survie sans progression et de la proportion de patientes sans progression de la maladie à 6 mois, d'un traitement combinant alpélisib et fulvestrant, et un traitement standard dans un contexte de vie réelle
Résumé en anglais
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) with an aromatase inhibitor (AI) as immediate prior therapy. Further analyses were performed to compare efficacy from BYLieve with effectiveness of standard treatment in the real‐world setting.
Patients and Methods: Patients who progressed on a CDK4/6i plus AI and were treated with alpelisib with fulvestrant in BYLieve were matched with a real‐world patient cohort who received standard of care from a de‐identified clinico‐genomics database (CGDB). Primary and secondary endpoints were to compare progression‐free survival (PFS), estimated by the Kaplan‐Meier method, and the proportion of patients remaining progression‐free at 6 months, respectively, between the 2 cohorts.
Results : A total of 855 patients with PIK3CA‐mutant disease who had prior CDK4/6i plus hormone therapy were selected from the CGDB; further matching to 120 patients from BYLieve selected 95 patients without exposure to HER2‐targeting agents, clinical study drug, or alpelisib. In unadjusted and post‐matching results, primary and secondary endpoints favored treatment with alpelisib with fulvestrant in BYLieve over standard treatments in the real‐world cohort. Post‐adjustment, median PFS for patients treated with alpelisib in BYLieve was 7.3 versus 3.7 months in the real‐world cohort, and 6‐month PFS was 54.6% versus 40.1%, respectively.
Conclusion : Matched/weighted analysis comparing BYLieve with the real‐world setting further supports the clinical benefit of alpelisib with fulvestrant for treatment of HR+, HER2−, PIK3CA‐mutant ABC post‐CDK4/6i treatment.
Implications for Practice : Approximately 40% of patients with hormone receptor‐positive (HR+), human epidermal growth factor receptor‐2–negative (HER2−) advanced breast cancer (ABC) have PIK3CA‐mutated tumors, which have been associated with endocrine therapy resistance. Alpelisib, an
