Mutations in PIK3CA are associated with poor prognosis in 28% to 46% of HR-positive/HER2-negative late-stage breast cancer. The SOLAR-1 study is a randomized, double-blind, placebo-controlled trial investigating the effectiveness of alpelisib (ALP), a PI3K-alpha selective inhibitor and degrader, in combination with fulvestrant (FUL) for treatment of HR-positive/HER2-negative advanced or metastatic breast cancer in patients with PIK3CA mutations. Phase 3 results of the study recently led to US Food and Drug Administration approval of the use of ALP in men and postmenopausal women.
Clinical and treatment profiles were available for 1579 participants. Tissue (35%) and liquid (31%) biopsy samples had PIK3CA mutations and 28% of tissue samples had SOLAR1 mutations (SOLAR1m), or activating mutations in exons 7, 9, and 20. In the tissues, 6.7% of samples with SOLAR1m had ≥1 lines additional mutations in other exons of the PIK3CA gene (OTHERm). Patients were grouped into 3 cohorts.
- Cohort A:
HR-positive/HER2-negative patients receiving FUL alone (n = 124) or ALP/FUL (n = 111) in ≥2 lines of therapy were considered in survival analysis. Real-world progression-free survival (PFS) was estimated from the start of treatment. Median real-world PFS was 4.1 months on FUL alone versus 6.5 months on combination ALP/FUL (P = .027) - Cohort B:
HR-positive/HER2-negative patients (n = 627) who received a clinical report with ALP listed. More SOLAR1m patients (39%) than OTHERm-only patients (27%) were treated with ALP. Patients with SOLARm received ALP treatment earlier - Cohort C:
patients with OTHERm only (n = 36), any receptor subtype, treated with ALP in any combination. Real-world PFS of >6 months was observed in 5 patients
Researchers conclude that ALP activity improves real-world PFS in patients with advanced breast cancer with PIK3CA mutations when used in combination with FUL compared with FUL alone. Patients with SOLAR1m received ALP treatment earlier than those with OTHERm. This study demonstrates the clinical relevance of ALP for improved prognosis in a diverse patient population.
Source: Rugo HS, Raskina K, Schrock AB, et al. Real-world (rw) clinical outcomes on alpelisib (ALP) in patients (pts) with breast cancer (BC) and PIK3CA mutations (PIK3CAm). American Society of Clinical Oncology Virtual Meeting; June 4-8, 2021. Abstract 1068.