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/m(2) 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.