A phase II study (BYLieve) has demonstrated the efficacy of alpelisib in combination with fulvestrant for treating advanced breast cancer with PIK3CA mutations. The research, published in The Lancet Oncology, highlights the potential of this therapeutic approach for patients who have progressed on prior CDK4/6 inhibitor and aromatase inhibitor therapy. This offers a new option for a subset of patients with limited alternatives.
The study, led by Rugo et al., enrolled 119 eligible patients across 18 countries between August 2017 and July 2022. These patients had hormone receptor-positive, HER2-negative advanced breast cancer with PIK3CA mutations. The treatment regimen consisted of alpelisib at 300 mg/day continuously, combined with fulvestrant at 500 mg intramuscularly on day 1 of each 28-day cycle, and on day 15 of cycle 1. The primary outcome measured was 6-month progression-free survival.
Efficacy and Outcomes
After a median follow-up of 21.8 months, the progression-free survival rate at 6 months was 53.8% (95% CI = 44.4%–63.0%), with 64 out of 119 patients alive without disease progression at 6 months. The median progression-free survival was 8.0 months (95% CI = 5.6–8.6 months), and the median overall survival was 27.3 months (95% CI = 21.3–32.7 months). Objective responses were observed in 23 patients (19%, 95% CI = 13%–28%), with a median duration of response of 13.8 months (95% CI = 5.5–19.4 months).
Safety Profile
The treatment regimen's safety profile revealed that grade ≥ 3 adverse events were reported in 69% of patients. The most common of these were hyperglycemia (29%), rash (10%), and maculopapular rash (9%). Serious adverse events occurred in 29% of patients, leading to treatment discontinuation in 23%. Notably, one death occurred during the study, but it was not attributed to the treatment.
Clinical Implications
The study's findings suggest that alpelisib plus fulvestrant is an effective treatment option for patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer, particularly after progression on a CDK4/6 inhibitor plus an aromatase inhibitor. According to the investigators, "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."
