Abstract OT2-06-02: A randomized phase II study of maintenance hormone therapy with or without capecitabine after induction therapy with bevacizumab plus paclitaxel in hormone receptor positive and HER2 negative metastatic breast cancer (KBCSG-TR1214)
Authors: Yamaguchi M , Nakayama T , Yoshinami T , Ikeda M , Iwamoto M , Komoike Y , Takashima T , Tsurutani J , Yoshidome K , Yamada T , Morita S , Masuda N 
Published: February 2018

Background: The combination therapy of Bevacizumab (B) and Paclitaxel (P) has proved to prolong progression free survival (PFS) in E2100 and MERiDiAN study for advanced and metastatic breast cancer(AMBC). Because of its longer PFS, developing optimal therapeutic strategy of B+P to improve survival, including management of toxicity is crucial. From the International Consensus Conference for Advanced Breast Cancer, most experts agreed the maintenance endocrine therapy after effective induction chemotherapy in AMBC. In KBCSG-TR 1214 study, we planned to examine the following clinical questions. 1. As a maintenance therapy, which is more effective either endocrine therapy alone (E) or endocrine therapy with capecitabine (E+C)? 2. Can maintenance therapy reduce toxicity of B+P and restore patient's QOL.? 3. How effective is B+P re-challenge after failure of maintenance therapy?

Methods: KBCSG-TR 1214 study is multicenter open-labeled randomized phase II trial for hormone receptor (HR)-positive and HER2-nagative patientswho have experienced none or one prior chemotherapy for AMBC. Patients will receive B (10mg/kg q2w) in combination with P (90mg/m2 on day 1, 8, and 15 q4w) as an induction therapy. Patients without progression after 6 cycles of B+P will be randomized to E or E+C. Endocrine treatment has been administrated by their physician's choice. Patients in E+C will receive endocrine therapy with capecitabine 1657mg/m2 on day1 to 21 q4w. Stratification factors for randomization are menopausal status, presence of target lesion, number of prior endocrine therapies for AMBC, with or without 1st line chemotherapy for AMBC. After progression of maintenance therapy (E or E+C), B+P will be started again as a re-challenge therapy. Primary end point is PFS of maintenance therapy. Secondary end points include time to failure of strategy from randomization, efficacy of re-challenge therapy, overall survival and safety of induction therapy. Translational research is also planned. VEGF, angiopoetin-1, and apelin in plasma will be measured at four points (before induction therapy, at the beginning of the maintenance therapy and the re-induction therapy, and at the end of the trial). The sample size was calculated by typeIerror (1-sided) of 0.05 and 80% power to estimate median PFS of each maintenance therapy 9 months with a threshold of 6 months. The target number of patients enrolled and randomized after induction therapy was 120 and 90, respectively.

Enrollment has been completed with 116 patients as of April, 2016 and 90 patients had been successful to shift to the maintenance phase with randomization. The last patient had been randomized on October, 2016. The first analysis will be planned during the second quarter of 2018 (UMIN000008662).

Citation Format: Yamaguchi M, Nakayama T, Yoshinami T, Ikeda M, Iwamoto M, Komoike Y, Takashima T, Tsurutani J, Yoshidome K, Yamada T, Morita S, Masuda N. A randomized phase II study of maintenance hormone therapy with or without capecitabine after induction therapy with bevacizumab plus paclitaxel in hormone receptor positive and HER2 negative metastatic breast cancer (KBCSG-TR1214) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-06-02.