Abstract P6-04-02: Final progression-free survival analysis of BOLERO-2: a phase III trial of everolimus for postmenopausal women with advanced breast cancer

Abstract

Abstract Introduction: Treatment options for postmenopausal women with hormone receptor-positive (HR+) breast cancer (BC) who relapse or progress on a nonsteroidal aromatase inhibitor (NSAI) are limited. Interim analyses of the BOLERO-2 trial demonstrated that combining the oral mammalian target of rapamycin (mTOR) inhibitor, everolimus (EVE), with the steroidal aromatase inhibitor, exemestane (EXE), significantly prolonged progression-free survival (PFS) in this patient population. Protocol-specified final PFS analyses are presented. Methods: The phase III, double-blind, BOLERO-2 trial randomized postmenopausal women with HR+ BC progressing or recurring after NSAIs to EVE (10 mg once daily; n = 485) plus EXE (25 mg once daily) or placebo (PBO; n = 239) plus EXE. The primary endpoint was PFS. Secondary endpoints included overall survival, safety, bone turnover, and overall response rate. Results: At a median follow-up of 18 months, 510 PFS events were reported. The addition of EVE to EXE significantly prolonged median PFS versus EXE monotherapy as per local assessment (7.8 vs 3.2 mo, respectively; HR = 0.45 [95% CI, 0.38–0.54]; log-rank P < .0001). Furthermore, these data were consistent with results based on central assessment (11.0 mo for EVE + EXE vs 4.1 mo for EXE alone; HR = 0.38 [95% CI, 0.31–0.48]; log-rank P < .0001). Fewer deaths were reported with EVE + EXE (25.4%) vs PBO + EXE (32.2%). In addition to significantly improving PFS and delaying disease progression in bone, PFS benefits with EVE + EXE versus PBO + EXE were consistent in all prospectively defined subgroups, including subsets of patients with visceral metastases (n = 406), 3 or more sites of metastasis (n = 271), and Eastern Cooperative Oncology Group (ECOG) performance status 1 or 2 (n = 274). The safety profile of EVE + EXE was consistent with that reported at the interim analysis and with data for EVE from other oncology settings. Updated overall survival data will be presented. Conclusions: Adding EVE to EXE markedly prolonged PFS in the overall population and in all patient subsets, validating the rationale of targeting the mTOR pathway to improve clinical outcome in patients with HR+ advanced BC progressing during or after NSAI therapy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-04-02.