Alpelisib Plus Fulvestrant for PIK3CA-Mutated, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2–Negative Advanced Breast Cancer: Final Overall Survival Results From SOLAR-1
Mené sur 341 hommes et femmes atteints d'un cancer du sein HR+ HER2- de stade avancé et présentant une mutation PIK3CA, cet essai évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité de l'ajout de l'alpéslisib au fulvestrant
Background : Activation of the phosphatidylinositol-3-kinase (PI3K) pathway via PIK3CA mutations occurs in 28%-46% of hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancers (ABC) and is associated with poor prognosis. The SOLAR-1 trial showed that the addition of alpelisib to fulvestrant treatment provided statistically significant and clinically meaningful progression-free survival (PFS) benefit in PIK3CA-mutated, HR+, HER2– ABC. Patients and Methods : Men and postmenopausal women with HR+, HER2– ABC whose disease progressed on or after aromatase inhibitor (AI) were randomized 1:1 to receive alpelisib (300 mg/day) plus fulvestrant (500 mg every 28 days and once on Day 15) or placebo plus fulvestrant. Overall survival (OS) in the PIK3CA-mutant cohort was evaluated by Kaplan-Meier methodology and a 1-sided stratified log-rank test was performed with an O’Brien-Fleming efficacy boundary of P≤0.0161. Results : In the PIK3CA-mutated cohort (n=341), median OS (95% confidence interval [CI]) was 39.3 months (34.1-44.9) for alpelisib-fulvestrant and 31.4 months (26.8-41.3) for placebo-fulvestrant (hazard ratio [HR] = 0.86 [95% CI, 0.64-1.15; P=0.15]). Overall survival results did not cross the prespecified efficacy boundary. Median OS (95% CI) in patients with lung and/or liver metastases was 37.2 months (28.7-43.6) and 22.8 months (19.0-26.8) in the alpelisib-fulvestrant and placebo-fulvestrant arms, respectively (HR=0.68 [0.46-1.00]). Median times to chemotherapy (95% CI) for the alpelisib-fulvestrant and placebo-fulvestrant arms were 23.3 months (15.2-28.4) and 14.8 months (10.5-22.6), respectively (HR=0.72 [0.54-0.95]). No new safety signals were observed with longer follow-up. Conclusions : Although the analysis did not cross the prespecified boundary for statistical significance, there was a 7.9-month numeric improvement in median OS when alpelisib was added to fulvestrant treatment for patients with PIK3CA-mutated, HR+, HER2– ABC. Overall, these results further support the statistically significant prolongation of PFS observed with alpelisib plus fulvestrant in this population, which has a poor prognosis due to a PIK3CA mutation.