UPDATED RESULTS OF THE BOLERO-2 PHASE III TRIAL EVALUATING EVEROLIMUS (EVE) FOR POSTMENOPAUSAL WOMEN WITH ADVANCED BREAST CANCER (ABC)

ABSTRACT Background The mTOR pathway is constitutively activated in hormone-resistant ABC. In phase II trials, EVE showed promising activity (monotherapy or + endocrine therapy) in pts with estrogen receptor-positive (ER+) ABC. This double-blind, placebo-controlled study evaluated EVE + exemestane (EXE) in pts with ER+ ABC refractory to nonsteroidal aromatase inhibitors (NSAI; letrozole or anastrozole). Patients and methods Eligible pts were randomized (2:1) to EXE (25 mg/day) + EVE (10 mg/day) or matching placebo (PBO). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, quality of life (QoL), and safety. Results 724 pts were randomized (485 EVE; 239 PBO). Baseline characteristics were well balanced: median age, 61 yr; visceral involvement, 59%; and documented benefit from previous endocrine therapy, 84% (NSAI [100%], tamoxifen [48%], fulvestrant [16%]), and chemotherapy for ABC (25%). This analysis includes 457 events and median follow-up of 12.5 mo. PFS by investigator assessment showed a hazard ratio (HR) of 0.44 (95% confidence interval [CI], 0.36 - 0.53) and a median duration of 7.4 (EVE) vs 3.2 mo (PBO; P Conclusion Adding EVE to EXE is associated with significant and sustained PFS prolongation in pts with NSAI-refractory ABC. Adverse events were higher with EVE but manageable by dose interruption/reduction and did not affect QoL. EVE combined with an AI is a promising therapeutic option for pts with ER+ ABC. Disclosure H. Rugo: Grants (paid to institution): Novartis; Pfizer; Merck Meetings/travel: Novartis. M. Piccart: Board Membership: PharmaMar Consultancy: sanofi-aventis, Amgen, BMS, GSK, Boehringer, Roche, Bayer Grants (paid to institution): Pfizer, Amgen, Bayer, GSK, Roche, sanofi-aventis Honoraria: Bayer, BMS, GSK, Boehringer, Roche, Amgen, sanofi-aventis. G. Hortobagyi: Consultancy: Novartis, Allergan, Genentech, sanofi-aventis Grants (paid to institution): Novartis Meetings/travel: Novartis, Genentech, sanofi-aventis S. Noguchi: Consultancy: Novartis Grants (paid to institution): Novartis Honoraria: Novartis. M. Gnant: Research Support: GlaxoSmithKline, sanofi-aventis, Novartis, Roche Consultancy: Merrion, Novartis Honoraria (Speaking, Advisory Boards, etc.) and Travel Support: Amgen, Pfizer, Novartis, GlaxoSmithKline, Bayer, Sandoz, AstraZeneca, GenomicHealth. M. Campone: Consultancy: Novartis Honoraria: Novartis. H. Bauly: Employment: Novartis Stocks: Novartis. P. Mukhopadhyay: Employment: Novartis Gnant: Novartis. T. Sahmoud: Employment: Novartis Stocks: Novartis. J. Baselga: Consultancy: Novartis, sanofi-aventis, Roche, Bayer, Merck, Verastem, Chugai, Exelixis, Onyx, Constellation.