In a cohort of a phase II study (BYLieve) reported in The Lancet Oncology, Rugo et al found that the PI3Kα inhibitor alpelisib plus the hormone therapy fulvestrant showed activity in patients with PIK3CA-mutated, hormone receptor–positive, HER2-negative advanced breast cancer after disease progression on a CDK4/6 inhibitor plus an aromatase inhibitor.
Study Details
The study cohort included 119 eligible patients with at least 18-month follow-up from sites in 18 countries enrolled between August 2017 and July 2022 (data cutoff). Patients received alpelisib at 300 mg/d (continuously) plus fulvestrant at 500 mg intramuscularly on day 1 of each 28-day cycle and on day 15 of cycle 1. The primary outcome measure was 6-month progression-free survival.
Key Findings
Median follow-up was 21.8 months (interquartile range = 10.8–37.6 months). Progression-free survival at 6 months was 53.8% (95% confidence interval [CI] = 44.4%–63.0%); 64 of 119 patients were alive without disease progression at 6 months.
Median progression-free survival was 8.0 months (95% CI = 5.6–8.6 months). Median overall survival was 27.3 months (95% CI = 21.3–32.7 months). Objective response was observed in 23 patients (19%, 95% CI = 13%–28%); median duration of response was 13.8 months (95% CI = 5.5–19.4 months).
Grade ≥ 3 adverse events were reported in 69% of patients, most commonly hyperglycemia (29%), rash (10%), and maculopapular rash (9%). Serious adverse events occurred in 29% of patients. Adverse events led to discontinuation of treatment in 23%. Adverse events led to one death, which was not considered to be related to treatment.
The investigators concluded: “BYLieve showed activity of alpelisib plus fulvestrant with manageable toxicity in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer, after progression on a CDK4/6 inhibitor plus an aromatase inhibitor.”
Hope S. Rugo, MD, of Breast Oncology and Clinical Trials Education, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Novartis Pharmaceuticals. For full disclosures of the study authors, visit thelancet.com.
