Phase III, randomized, double-blind, placebo-controlled multicenter trial of daily everolimus plus weekly trastuzumab and vinorelbine in trastuzumab-resistant, advanced breast cancer (BOLERO-3).

Abstract

505 Background: Everolimus (EVE) is an inhibitor of mammalian target of rapamycin (mTOR), a protein kinase central to a number of signaling pathways regulating cell growth and proliferation. Data from preclinical and phase 1/2 clinical studies indicated that adding EVE to trastuzumab (TRAS) plus chemotherapy may restore sensitivity to and enhance efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapy. The international BOLERO-3 phase 3 study is being conducted to evaluate the addition of EVE to TRAS plus vinorelbine. Methods: Adult women with HER2+ advanced breast cancer and who received prior taxane therapy and experienced recurrence or progression on TRAS were randomized 1:1 to receive either EVE or placebo (5 mg/day) in combination with weekly TRAS and vinorelbine (25 mg/m2). The primary endpoint is progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, safety, quality of life, and pharmacokinetics. Final analysis will be conducted after approximately 417 PFS events. Results: The trial accrued 569 patients between October 2009 and May 2012. Previous therapy included TRAS (100%), a taxane (100%), and lapatinib (28%). The median age was 54 years, and 76% of patients had visceral metastases, 5% had stable brain metastases, 56% had hormone-receptor–positive disease, 33% had Eastern Cooperative Oncology Group performance status of 1 or 2, and 41% had 3 or more metastatic sites. The median number of prior chemotherapy lines in the metastatic setting was 1. As of February 4, 2013, a total of 396 PFS events were reported. Conclusions: Final PFS analysis will be performed in early May 2013; primary and secondary efficacy endpoints will be presented. Clinical trial information: NCT01007942.