Patients with breast cancer and PIK3CA mutations who receive alpelisib plus fulvestrant have longer real-world progression-free survival (PFS) compared with those who receive fulvestrant alone, according to a study presented at the virtual 2021 ASCO Annual Meeting.

“[Alpelisib] was approved by the FDA for treatment of HR+/HER2- advanced breast cancer with activating PIK3CA [mutation] based on the phase 3 SOLAR-1 trial,” explained Hope S. Rugo, FASCO, MD, University of California, San Francisco, San Francisco, and colleagues.

This study aimed to assess the prevalence of PIK3CA gene mutations and report real-world clinical outcomes of treatment with alpelisib in this patient population.

A total of 31,765 results from comprehensive genomic profiling and 4147 liquid biopsies from patients with breast cancer were analyzed. Clinical characteristics and treatment history were available for 1579 patients with PIK3CA gene mutations in a de-identified Flatiron Health-Foundation Medicine clinic-genomic database.

Three cohorts were considered in the analysis: Patients receiving fulvestrant alone (n = 124) or alpelisib plus fulvestrant (n = 111) for second- or later-line treatment (cohort A); patients who received a clinical report with alpelisib listed after May 2019 (n = 627, cohort B); and patients with activating mutation elsewhere on the PIK3CA gene than that in the SOLAR-1 trial, any receptor subtype, treated with alpelisib in any combination (n = 36, cohort C).

Cohort A was considered in the survival analysis. Kaplan-Meier analysis was used to estimate real-world PFS from the start of treatment. Hazard ratios from Cox proportional hazards models adjusted for survival bias.

Among the 31,765 tissue biopsies, 10,869 (34%) had a PIK3CA mutation. Of these mutations, 8750 (28%) had mutations in PIK3CA exons 7, 9, and 20, 1146 of which had ≥1 additional other PIK3CA mutation. In addition, 2119 had ≥1 other PIK3CA mutation with any mutations in PIK3CA exons 7, 9, and 20.

The most common other mutations in the presence of a mutation in PIK3CA exons 7, 9, and 20 were E726K, E418K, E365K, E453Q, and H1048R (P <.0001). The most common other mutations without the presence of a mutation in PIK3CA exons 7, 9, and 20 were N345K, G1049R, Q546K, and indels disrupting PIK3R1 binding (P <.0001).

Detection rates with liquid biopsies were comparable to tissue biopsies. Among the 4147 liquid biopsies, 1391 (34%) had a PIK3CA mutation. Of these mutations, 8750 (28%) had mutations in PIK3CA exons 7, 9, and 20.

The median real-world PFS in cohort A was 4.1 months with fulvestrant vs 6.5 months with fulvestrant plus alpelisib (P = .027).

In cohort B, 39% of patients with mutations in PIK3CA exons 7, 9, and 20 were treated with alpelisib compared with 27% of patients with other mutations only. In addition, patients with with mutations in PIK3CA exons 7, 9, and 20 received alpelisib in earlier treatment lines compared with those other mutations.

In cohort C, real-world PFS >6 months was reported for 5 patients with N345K, Q75E, R38C, G106_108del, and N345K/N1044K.

“This study validates the activity of alpelisib among a diverse real-world population, showing patients with PIK3CA mutations have longer real-world PFS on alpelisib/fulvestrant than fulvestrant alone,” Dr Rugo and colleagues concluded.—Janelle Bradley

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). Presented at: the 2021 ASCO Annual Meeting; June 4-8, 2021; virtual. Abstract 1068.