Background: Although there is no single accepted standard of care after failure of anthracycline and taxane therapy in HER2-negative metastatic breast cancer, capecitabine is a well-established treatment option. Bendamustine is a hybrid cytotoxic drug because of its structural similarity to alkylating agents and purine and it is generally well tolerated. Since bendamustine has already shown anticancer activity in breast cancer we evaluated the efficacy and tolerability of bendamustine in combination with capecitabine in 40 patients with advanced breast cancer after anthracycline and/or taxane pretreatment.

Patients and methods: MBC-6 is a non-randomized, multicenter, open-label, single-arm phase II study in patients with HER2-negative advanced breast cancer (ClinicalTrials.gov identifier: NCT01891227). All patients were pretreated with anthracyclines and/or taxans in the (neo-)adjuvant and/or metastatic setting and measurable disease according to RECIST 1.1. had to be present at baseline. Following a two-stage Green-Dahlberg design, 20 subjects were accrued and treated within stage 1 of the study. The trial was planned to enroll further 20 patients if there were at least four subjects (20%) with a complete (CR) or partial response (PR). Eligible patients received 1000 mg/m2 capecitabine twice daily on days 1 to 14 in combination with 80 mg/m2 bendamustine on day 1 and 8 of a 3-week cycle. After a maximum of eight cycles capecitabine was continued as single drug therapy until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Secondary endpoints were progression free survival (PFS), clinical benefit rate (CBR), safety profile and quality of life. Here we report the efficacy and safety analysis of stage 1 patients.

Results: From September 2013 to May 2015, 40 patients were recruited in eight Austrian centers. Median age of the stage 1 cohort was 59 years (range 29-77), 80% and 20% of patients had an ECOG performance score of 0 and 1, respectively. Thirty-three percent had triple-negative disease, 85% had had (neo-)adjuvant treatment and 65% patients were pretreated with at least one chemotherapy line for metastatic disease (15% one line, 50% two lines, 40% three lines). In stage 1, ORR was 50% with 9 confirmed PR and 1 confirmed CR, and ORR was comparable between hormone receptor-positive and triple-negative disease (54% vs. 43%). CBR was 55%. At data cut-off on 05/28/15 overall 15 of 20 patients had discontinued treatment: 10 patients (50%) due to progressive disease, 3 (15%) because of adverse events (AEs) and 2 patients on their own decision (10%). Five patients (25%) experienced at least one drug related non-hematological AE ≥ grade 3: 2 diarrhea, 2 fatigue, 3 respiratory or viral infections, 1 dyspnea, 1 thromboembolic event (each grade 3). One grade 4 hematological AE (neutropenia) was observed. One patient died as a result of restrictive cardiomyopathy, where a relationship to capecitabine cannot be excluded, but seems unlikely.

Conclusion: The combination of capecitabine and bendamustine has a moderate toxicity profile and the response data of the stage 1 are promising. Final study results are awaited in the first half of 2016.

Citation Format: Rinnerthaler G, Gampenrieder SP, Fridrik M, Petzer A, Hubalek M, Petru E, Jäger T, Andel J, Balic M, Ulmer H, Mlineritsch B, Greil R. Capecitabine in combination with bendamustine in pretreated women with HER2-negative metastatic breast cancer: Stage 1 results of a phase II trial (AGMT MBC-6). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-13-10.