Capecitabine in combination with bendamustine in pretreated women with HER2-negative metastatic breast cancer: results of a phase II trial (AGMT MBC-6)

Gabriel Rinnerthaler, Simon Peter Gampenrieder, Andreas Petzer, Michael Hubalek, Edgar Petru, Margit Sandholzer, Johannes Andel, Marija Balic, Thomas Melchardt, Cornelia Hauser-Kronberger, Clemens A Schmitt, Hanno Ulmer, Richard Greil, Gabriel Rinnerthaler, Simon Peter Gampenrieder, Andreas Petzer, Michael Hubalek, Edgar Petru, Margit Sandholzer, Johannes Andel, Marija Balic, Thomas Melchardt, Cornelia Hauser-Kronberger, Clemens A Schmitt, Hanno Ulmer, Richard Greil

Abstract

Background: Bendamustine, a medication approved for the treatment of indolent non-Hodgkin lymphoma, has already shown anticancer activity in metastatic breast cancer (MBC). Here, we present the results of a phase II trial of bendamustine in combination with capecitabine in pre-treated patients with MBC.

Patients and methods: AGMT MBC-6 is a multicentre, open-label, single-arm phase II study in HER2-negative MBC. All patients were pre-treated with anthracyclines and/or taxans and had measurable disease. Patients received per os 1000 mg/m2 capecitabine twice daily on days 1 to 14 in combination with 80 mg/m2 bendamustine intravenously on days 1 and 8 of a 3-week cycle for a maximum of eight cycles, followed by a capecitabine maintenance therapy. The primary endpoint was overall response rate (ORR).

Results: From September 2013 to May 2015, 40 patients were recruited in eight Austrian centres. The median age was 60 years (range 29-77). Twenty-five per cent of patients had triple-negative breast cancer (TNBC) and 93% showed visceral involvement. With 17 partial and one complete remission, ORR was 46%. Median progression-free survival (PFS) was 7.5 months [95% confidence interval (CI) 6.1-10.7]. The most common non-haematological adverse events (AEs) of grade 3 were hand-foot syndrome (13%), fatigue (10%), nausea (8%), and dyspnoea (8%). One grade 4 non-haematological AE (hepatic failure) and three grade 4 haematological AEs (neutropenia) were observed. One patient died of restrictive cardiomyopathy, in which a relationship to capecitabine cannot be excluded, but seems unlikely.

Conclusion: The combination of capecitabine and bendamustine shows promising efficacy and moderate toxicity. Further evaluation of this drug combination is warranted.The clinical trial AGMT MBC-6 was registered at ClinicalTrials.gov, (https://ichgcp.net/clinical-trials-registry/NCT01891227" title="See in ClinicalTrials.gov">NCT01891227).

Keywords: advanced breast cancer; chemotherapy; combination therapy.

Conflict of interest statement

Conflict of interest statement: Conflicts of interest with Mundipharma: Employment or leadership position: none; Consultant or advisory role: Andreas Petzer, Richard Greil; Fees for non-CME services received directly from commercial interest or their agents: none; Contracted research: Richard Greil; Ownership interest: none; Traveler grants: none.

© The Author(s), 2021.

Figures

Figure 1.
Figure 1.
CONSORT diagram. Response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI) every 9 weeks throughout therapy. A central review of CT or MRI scans was established for participating sites which could not provide assessments according to response evaluation criteria in solid tumours (RECIST) 1.1. Treatment decisions were made according to local CT/MRI reports.
Figure 2.
Figure 2.
Progression free survival. Progression free survival (a) in the overall population, (b) by receptor status, (c) and by thymidylate phosphatase expression in patients who received capecitabine and bendamustine combination therapy. HR, hormone receptor; TNBC, triple negative breast cancer; TP, thymidine phyosphorylase.

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