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

Dana M. Roque, Division of Gynecologic Oncology, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Eric R. Siegel, Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Natalia Buza, Department of Pathology, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Stefania Bellone, Division of Gynecologic Oncology, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Gloria S. Huang, Division of Gynecologic Oncology, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Gary Altwerger, Division of Gynecologic Oncology, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Vaagn Andikyan, Division of Gynecologic Oncology, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Mitchell Clark, Division of Gynecologic Oncology, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Masoud Azodi, Division of Gynecologic Oncology, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Peter E. Schwartz, Division of Gynecologic Oncology, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Gautam G. Rao, Division of Gynecologic Oncology, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Elena Ratner, Department of Pathology, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Alessandro D. Santin, Department of Pathology, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA. alessandro.santin@yale.edu.

Document Type

Article

Publication Title

BJC reports

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 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.

First Page

43

DOI

10.1038/s44276-024-00067-5

Publication Date

6-20-2024

Identifier

39516558 (pubmed); PMC11523995 (pmc); 10.1038/s44276-024-00067-5 (doi); 10.1038/s44276-024-00067-5 (pii)

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