Abstract P2-15-01: A randomized, multicenter, phase II study evaluating the efficacy of interventional maintenance endocrine therapy with bevacizumab following fixed cycles of bevacizumab plus paclitaxel in advanced/metastatic ER-positive HER2-negative breast cancer: JBCRG-M04 BOOSTER trial
Authors: Saji Shigehira , Kitada Masahiro , Takano Toshimi , Takada Masahiro , Ohtake Tohru , Toyama Tatsuya , Kikawa Yuichiro , Hasegawa Yoshie , Fujisawa Tomomi , Kashiwaba Masahiro , Ishida Takanori , Nakamura Rikiya , Yamamoto Yutaka , Toh Uhi , Iwata Hiroji , Masuda Norikazu , Taira Naruto , Morita Satoshi , Ohno Shinji , Toi Masakazu 
Published: March 2020

Abstract
Background: The standard chemotherapy treatment strategy for patients with advanced/metastatic breast cancer (ABC) is the continuation of the same drug until tumor progression. However, despite continued antitumor effects, continuation of a drug often becomes difficult because of cumulative adverse events, such as peripheral neuropathy.
Methods: This multicenter, randomized, Phase II study in patients with estrogen receptorpositive (ER+) human epidermal growth factor receptor 2-negative (HER2−) ABC aimed to compare 2 treatment strategies following induction therapy with 4-6 cycles of the combined use of weekly paclitaxel (wPTX) and bevacizumab (BV). Patients in Arm A continued with wPTX+BV, whereas patients in Arm B were switched from wPTX to maintenance endocrine therapy (endocrine+BV) until disease progression, followed by wPTX+BV re-induction. The primary endpoint was time to failure of strategy (TFS), defined as the time from randomization to a qualifying event (addition of a new agent not in the primary regimen, progressive disease during or after planned therapy, or death). Secondary endpoints were overall survival (OS), progression-free survival, safety, and quality of life (QoL). Sequential plasma and serum biomarkers were analyzed for predicting/monitoring the response.
Result: Of 160 patients enrolled to receive induction therapy with wPTX+BV, 125 patients responded to treatment (complete response [CR], partial response [PR], or stable disease) and were randomized to either of the 2 treatment arms. Median follow-up was 21.3 months. Aromatase inhibitor (AI), fulvestrant, or AI with a luteinizing hormonereleasing hormone (LH-RH) analogue was used as maintenance endocrine therapy. The primary endpoint of TFS was 8.87 months (95% CI: 5.68-13.80) in the wPTX+BV continued group (Arm A) and 16.82 months (95% CI: 12.88-18.99) in the maintenance endocrine+BV group (Arm B) (hazard ratio [HR], 0.51; p&lt;0.001). In Arm B, 52% of patients received wPTX+BV re-induction upon progression with maintenance therapy. Although the OS data were not yet mature, a trend of OS benefit was noted in a subset of patients in the maintenance group (Arm B) who achieved an objective response (CR or PR) to induction chemotherapy (HR, 0.75; 95% CI: 0.34-1.62). Health-related QoL data and biomarker analysis with IMPACT assay will be presented at the symposium.
Conclusion: This is the first study showing the benefit of maintenance endocrine therapy in patients with ER+ HER2− advanced breast cancer who responded to a fixed dose of chemotherapy. (UMIN: UMIN000012179; ClinicalTrials.gov: NCT01989780)
Funding: Chugai Pharmaceutical CO., LTD.
Citation Format: Shigehira Saji, Masahiro Kitada, Toshimi Takano, Masahiro Takada, Tohru Ohtake, Tatsuya Toyama, Yuichiro Kikawa, Yoshie Hasegawa, Tomomi Fujisawa, Masahiro Kashiwaba, Takanori Ishida, Rikiya Nakamura, Yutaka Yamamoto, Uhi Toh, Hiroji Iwata, Norikazu Masuda, Naruto Taira, Satoshi Morita, Shinji Ohno, Masakazu Toi. A randomized, multicenter, phase II study evaluating the efficacy of interventional maintenance endocrine therapy with bevacizumab following fixed cycles of bevacizumab plus paclitaxel in advanced/metastatic ER-positive HER2-negative breast cancer: JBCRG-M04 BOOSTER trial [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 P2-15-01.