Abstract P5-15-13: Capecitabine in combination with bendamustine in pretreated women with HER2-negative metastatic breast cancer: Final PFS results of a phase II trial (AGMT MBC-6)
Authors: G Rinnerthaler, SP Gampenrieder, D Voskova, A Petzer, M Hubalek, E Petru, B Hartmann, J Andel, M Balic, T Melchardt, H Ulmer, B Mlineritsch, R Greil
Journal: Cancer Research (2017)

Abstract Background: 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 pretreated patients with ABC. Here we present the final PFS results of this phase II trial. Patients and methods: MBC-6 is a non-randomized, multicenter, open-label, single-arm phase II study in patients with HER2-negative ABC (ClinicalTrials.gov: NCT01891227). All patients were pretreated with anthracyclines and/or taxans and had measurable disease according to RECIST 1.1. 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 for a maximum of 6 cycles. Afterwards capecitabine was continued as monotherapy. The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), clinical benefit rate (CBR), safety and quality of life. Results: From September 2013 to May 2015, 40 patients were recruited in eight Austrian centers. Median age was 60 years (range 29-77). Twenty-five percent of patients had triple-negative disease (TNBC) and 93% showed visceral involvement. Sixty-five percent had received prior chemotherapy in the (neo)adjuvant setting and 63% for ABC (43% one line, 15% two lines, 5% three lines). All patients with ER-positive disease had received prior endocrine therapy.At data cut-off on 06/08/16 overall 39 of 40 patients had discontinued treatment with a median PFS of 7.0 months (95% CI 4.6-9.5), 7.4 months in ER-positive and 4.0 months in triple negative disease (TNBC), respectively. Twelve patients (30%) experienced at least one drug related non-hematological AE ≥ grade 3 during combination treatment and further 6 patients (15%) during capecitabine maintenance. Three grade 4 hematological AEs (neutropenia) were 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 shows promising efficacy and a moderate toxicity profile. Further evaluation of this drug combination is warranted.Background: 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 pretreated patients with ABC. Here we present the final PFS results of this phase II trial. Patients and methods: MBC-6 is a non-randomized, multicenter, open-label, single-arm phase II study in patients with HER2-negative ABC (ClinicalTrials.gov: NCT01891227). All patients were pretreated with anthracyclines and/or taxans and had measurable disease according to RECIST 1.1. 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 for a maximum of 6 cycles. Afterwards capecitabine was continued as monotherapy. The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), clinical benefit rate (CBR), safety and quality of life. Results: From September 2013 to May 2015, 40 patients were recruited in eight Austrian centers. Median age was 60 years (range 29-77). Twenty-five percent of patients had triple-negative disease (TNBC) and 93% showed visceral involvement. Sixty-five percent had received prior chemotherapy in the (neo)adjuvant setting and 63% for ABC (43% one line, 15% two lines, 5% three lines). All patients with ER-positive disease had received prior endocrine therapy.At data cut-off on 06/08/16 overall 39 of 40 patients had discontinued treatment with a median PFS of 7.0 months (95% CI 4.6-9.5), 7.4 months in ER-positive and 4.0 months in triple negative disease (TNBC), respectively. Twelve patients (30%) experienced at least one drug related non-hematological AE ≥ grade 3 during combination treatment and further 6 patients (15%) during capecitabine maintenance. Three grade 4 hematological AEs (neutropenia) were 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 shows promising efficacy and a moderate toxicity profile. Further evaluation of this drug combination is warranted. Citation Format: Rinnerthaler G, Gampenrieder SP, Voskova D, Petzer A, Hubalek M, Petru E, Hartmann B, Andel J, Balic M, Melchardt T, Ulmer H, Mlineritsch B, Greil R. Capecitabine in combination with bendamustine in pretreated women with HER2-negative metastatic breast cancer: Final PFS results of a phase II trial (AGMT MBC-6) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-15-13.