Correlation of PIK3CA mutations in cell-free DNA (cfDNA) and efficacy of everolimus (EVE) in metastatic breast cancer: Results from BOLERO-2.

519Background: PIK3CA is the most commonly mutated gene in metastatic HR+ breast cancer but its impact on the clinical efficacy of mTOR inhibitor EVE and endocrine therapies is not fully established. We analyzed cfDNA for PIK3CA hotspot mutations to determine their impact on the clinical benefit of exemestane (EXE) or EXE plus EVE from the BOLERO-2 trial that randomized patients (pts) to these two treatment arms (2:1). Methods: Baseline plasma samples were analyzed by ddPCR for H1047R, E545K, and E542K mutations (~85% of activating PIK3CAmutations). Cox-proportional hazards model was used to assess PFS in pt subgroups defined by all or domain specific mutations separately (E545K/E542K for helical and H1047R for kinase domain). Results: 550 of 724 pts (76% trial population) had evaluable genotype results. 238 (43.3%) mutations were identified with frequencies of 25.3%, 11.3% and 7.5% for H1047R, E545K and E542K, respectively. Among 247 pts with PIK3CA genotype derived from sequencing matched archival tumor...