Randomized phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer (NCT03093155): Updated survival and subgroup analyses

Abstract

Abstract Background Ixabepilone may retain activity in paclitaxel-resistant disease. We previously reported improved response rates (ORR), progression-free (PFS), and overall survival (OS) conferred by ixabepilone+bevacizumab (IXA + BEV) compared to monotherapy (IXA) in heavily pre-treated ovarian cancers. We now describe a mature data set. Subset analyses were performed in patients with different taxane sensitivities and dose modifications. Methods Patients previously treated with paclitaxel were stratified by prior BEV and randomized to receive IXA 20 mg/m2 days 1,8,15 ± BEV 10 mg/kg days 1,15 of a 28-day cycle in a multi-site prospective randomized phase 2 trial. Results Thirty-seven patients were randomized to IXA and 39 patients to IXA + BEV. At the final data cutoff (05/27/2023), ORR was higher in the IXA + BEV arm (38.4% vs. 8.1%, p = 0.003). Dose reductions were necessary in most participants but did not diminish PFS/OS benefits. Most patients were paclitaxel-refractory/-resistant (51%, n = 19/37;67%, n = 26/39); the remainder were taxane-sensitive. The addition of BEV to IXA conferred benefit in PFS (5.5 vs. 2.2 mo; HR 0.31, 90%CI 0.20–0.49, p < 0.001) and OS (10.3 vs. 6.0 mo; HR 0.56, 90%CI 0.38–0.84, p = 0.02) that persisted after adjusting for prior taxane response. Conclusions IXA + BEV has activity in heavily pre-treated ovarian cancers and offers significant improvement in ORR and PFS/OS compared to IXA, despite prior taxane response and dose reductions. Clinical Trial Registration NCT03093155