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).

Breast Cancer - HER2/ER
Session Type and Session Title: 
Oral Abstract Session, Breast Cancer - HER2/ER
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 505)
Ruth O'Regan, Mustafa Ozguroglu, Fabrice Andre, Masakazu Toi, Guy Heinrich Maria Jerusalem, Sharon Wilks, Claudine Isaacs, Binghe Xu, Norikazu Masuda, Francis P. Arena, Denise Aysel Yardley, Yoon Sim Yap, Pabak Mukhopadhyay, Shyanne Douma, Mona El-Hashimy, Tanya Taran, Tarek Sahmoud, David Edward Lebwohl, Luca Gianni; Georgia Cancer Center for Excellence at Grady Memorial Hospital, Atlanta, GA; Istanbul University, Istanbul, Turkey; Institut Gustave Roussy, Villejuif, France; Graduate School of Medicine Kyoto University, Kyoto, Japan; Centre Hospitalier Universitaire Sart Tilman Liege and University of Liege, Liège, Belgium; Cancer Care Centers of South Texas, San Antonio, TX; Lombardi Comprehensive Cancer Center, Washington, DC; Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China; NHO Osaka National Hospital, Osaka, Japan; Arena Oncology Associates, Lake Success, NY; Sarah Cannon Research Institute; Tennessee Oncology, Nashville, TN; National Cancer Centre Singapore, Singapore, Singapore; Novartis Pharmaceuticals Corp, East Hanover, NJ; Novartis Pharmaceuticals, East Hanover, NJ; Novartis Pharmaceuticals, Florham Park, NJ; Global Oncology Development, Novartis Pharmaceuticals Corporation, Florham Park, NJ; San Raffaele Scientific Institute, Milan, Italy

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Abstract Disclosures


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.