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

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