Capecitabine is a well-established treatment option in HER2-negative advanced breast cancer (ABC) patients. Bendamustine is a generally well tolerated cytotoxic drug. Since bendamustine has already shown anticancer activity in ABC we evaluated the efficacy and tolerability of bendamustine in combination with capecitabine in 40 pretreated patients with ABC.
MBC-6 is a non-randomized, multicenter, open-label, single-arm phase II study in patients with HER2-negative ABC (ClinicalTrials.gov identifier: NCT01891227). All patients were pretreated with anthracyclines and/or taxans and measurable disease according to RECIST 1.1. had to be present at baseline. 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. Efficacy results have been presented at the ASCO Annual Meeting 2016, Abstr 1032. Here we report the updated safety analysis.
From September 2013 to May 2015, 40 patients were recruited in 8 Austrian centers. At data cut-off on 05/02/16 overall 37 of 40 patients had discontinued treatment: 25 (68%) due to progressive disease, 4 (11%) because of adverse events (AEs), 7 (18%) on their own or investigator decision and 1 (3%) due to protocol violation. Twelve patients (30%) experienced at least one drug related non-hematological AE ≥ grade 3 during combination treatment (2 infections, 1 erysipelas, 5 fatigue, 4 thromboembolic events, 2 diarrhea, 1 nausea, 1 emesis, 1 constipation, 1 syncope, 1 polyneuropathy, 1 stomatitis, 1 hand-foot syndrome, each grade 3) and further 6 patients (15%) during capecitabine maintainance (3 infections, 3 diarrhea, and 4 hand-foot syndroms, each grade 3). Three grade 4 hematological AEs (neutropenias) were observed. One patient died as a result of restrictive cardiomyopathy, where a relationship to capecitabine cannot be excluded, but seems unlikely.
The combination of capecitabine and bendamustine has a moderate toxicity profile. Final study results are awaited later in 2016.
Clinical trial identification
ClinicalTrials.gov identifier: NCT01891227
Legal entity responsible for the study
AGMT (Arbeitsgemeinschaft medikamentöse Tumortherapie - Study Group of Medical Tumour Therapy) Wolfsgartenweg 31 5026 Salzburg, Austria
This research was supported in part by a Research Grant from Mundipharma®
A. Petzer: Conflicts of Interest with Mundipharma®: Fees for non-CME services received directly from commercial interest or their agents and Traveler Grants. E. Petru, R. Greil: Conflicts of Interest with Mundipharma®: Fees for non-CME services received directly from commercial interest or their agents.
J. Andel: Conflicts of Interest with Mundipharma®: Consultant or Advisory Role. M. Balic: Conflicts of Interest with Mundipharma®: Consultant or Advisory Role and Traveler Grants. B. Mlineritsch: Conflicts of Interest with Mundipharma®: Consultant or Advisory Role, and Fees for non-CME services received directly from commercial interest or their agents. All other authors have declared no conflicts of interest.