Abstract P5-19-06: 4EVER - Final efficacy analysis of the phase IIIb, multi-center, open label study for postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer (BC) treated with everolimus (EVE) in combination with exemestane (EXE)

Introduction: The phase III BOLERO-2 trial showed a significant doubling of PFS benefit with EVE + EXE over EXE alone in postmenopausal women with hormone receptor positive advanced BC progressing after non-steroidal aromatase inhibitor (NSAI) therapy. The 4EVER trial further evaluated the combination of EVE+EXE with regard to efficacy and safety, quality of life and health resources utilization in a broader patient population, i.e. without limitations as to the number of previous chemotherapy lines, the time point of progression after NSAI therapy, and the previous EXE therapy. Methods: From May 2012 to November 2012 a total of 299 postmenopausal women with metastatic or locally advanced, hormone receptor positive, HER2 negative breast cancer, refractory to NSAI were recruited to this phase IIIb study. Here we report the results of the planned analysis of the primary and secondary endpoints. The primary endpoint was the overall response rate (ORR) at week 24. The secondary endpoints included: Progression-free survival (PFS), ORR at week 48, overall survival (OS), and quality of life. This study includes a broad exploratory translational research program e.g. changes in serum bone turnover biomarkers, the correlation of Interleukin-6 with anxiety and depression, presence and molecular characteristics of circulating tumor cells, the correlation of response to EXE+EVE with pharmacogenomics. Results: Trial database lock will occur in late June 2014, therefore, the final data concerning the primary and secondary efficacy and safety endpoints will be presented at SACBS 2014. The preliminary baseline analysis included 299 patients (data cut off 15 Nov 2013): HR status: ER+/PgR+ 78.1%, ER+/PgR- 20.9%, 0.7% ER-/PgR+, 0.3% ER-/PgR-. Tissue for receptor status analysis: 71.0% primary tumor, 29.0% metastasis. The mean time since initial diagnosis was 9.6 years, the mean time since first relapse/metastasis was 4.3 years. The mean time since last relapse/metastasis was 2.8 months. 68.1% of patients had bone lesions. Last anti-neoplastic therapy had been administered in the adjuvant (23.9%) and metastatic setting (73.0%). 25.9% of patients had no prior antineoplastic therapy in the metastatic setting, 16.3% had one, 12.2% two and 47.4% three or more prior therapies. Conclusion: The final analysis of the 4EVER study provides more important information on disease patterns and benefits of the combined treatment with EVE and EXE. Citation Format: Hans Tesch, Oliver J Stoetzer, Thomas Decker, Christian M Kurbacher, Romy Neumeister, Frederik Marme, Andreas Schneeweis, Christoph Mundhenke, Andrea Distelrath, Peter A Fasching, Michael P Lux, Diana Lueftner, Peyman Hadji, Wolfgang Janni, Mathias Muth, Julia Kreuzeder, Claudia Weiss, Diethelm Wallwiener. 4EVER - Final efficacy analysis of the phase IIIb, multi-center, open label study for postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer (BC) treated with everolimus (EVE) in combination with exemestane (EXE) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-19-06.