Abstract P3-12-01: Addition of capecitabine to maintenance endocrine therapy after induction therapy with bevacizumab plus paclitaxel in hormone receptor positive and HER2 negative metastatic breast cancer (KBCSG-TR1214)

Background: In the International Consensus Conference Guidelines for Advanced Breast Cancer, most experts agreed that the maintenance endocrine therapy after induction chemotherapy was reasonable. The combination therapy of bevacizumab (B) and paclitaxel (P) has proved to prolong progression free survival (PFS) and improve response rate in E2100 and MERiDiAN study for advanced and metastatic breast cancer (AMBC). Because of its long PFS, developing optimal therapeutic strategy of B+P to improve survival, including management of toxicity is crucial. However, it has not been assessed what therapy is optimal as maintenance therapy or how effective B+P re-challenge after failure of maintenance therapy is. Methods: In this multi-center randomized phase II study (KBCSG-TR1214), we compared endocrine therapy alone (E) and endocrine therapy with capecitabine (E+C) as a maintenance therapy after the induction chemotherapy with B+P. .Hormone receptor (HR)-positive and HER2-nagative patients who have experienced none or one prior chemotherapy for AMBC were enrolled. Patients without progression in 4-6 cycles of B+P were randomized to arm E (with E) or arm E+C (with E+C). In both arms, endocrine agents were decided by physician’s choice and in arm E+C, capecitabine (1657mg/m2 on day1 to 21 q4w) was added to E. After progression of either maintenance therapies, B+P started again as a re-challenge therapy. Primary end point was progression free survival (PFS) of maintenance therapy. Secondary end points include time to failure of strategy from randomization (TFS), efficacy of re-challenge therapy, overall survival (OS) and safety of induction therapy. Results:116 patients were enrolled until April 2016. 90 patients had been successful to shift to randomization. Median age was 59.8 years-old (34-81). 28 (60.9%) of 46 patients in arm E and 27 (61.4%) of 44 patients in arm E+C were administrated by aromatase inhibitor (AI) or AI+LH-RH analog. Median PFS of maintenance therapy was significantly longer in arm E+C (11.3month, 95%CI; 8.0-11.8) than in arm E (4.3months, 95%CI; 3.6-6.0) (HR:0.53, p=0.0054). Clinical benefit rate was 50.0% in arm E and 72.7% in arm E+C (p=0.0320). Median PFS, objective response rate and clinical benefit rate of P+B as re-challenge therapy following either E or E+C were 7.8months (95%CI; 6.7-9.5), 20.4% and 63.0%, respectively. There was a strong trend of improvement in OS at 24 months from randomization in arm E+C (73.0%) compared with in arm E (53.1%) (p=0.0524). We have not observed any new adverse toxicity profile regarding to E or E+C. Conclusions: Adding capecitabine to maintenance endocrine therapy was demonstrated to improve PFS and OS. To our knowledge, this is the first clinical trial to show the efficacy of endocrine therapy combined with metronomic chemotherapy as maintenance therapy after induction chemotherapy in HR-positive and HER2-negative AMBC patients. The concept of induction-maintenance could be a new therapeutic strategy for ABMC. (UMI08662). Citation Format: Tetsuhiro Yoshinami, Takahiro Nakayama, Masahiko Ikeda, Makiko Mizutani, Miki Yamaguchi, Yoshifumi Komoike, Tsutomu Takashima, Katsuhide Yoshidome, Junji Tsurutani, Mitsuhiko Iwamoto, Fumie Fujisawa, Hiroyuki Yasojima, Jun Yamamura, Hirotaka Morishima, Fuminori Aki, Tomomi Yamada, Satoshi Morita, Norikazu Masuda. Addition of capecitabine to maintenance endocrine therapy after induction therapy with bevacizumab plus paclitaxel in hormone receptor positive and HER2 negative metastatic breast cancer (KBCSG-TR1214) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-12-01.