Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer

Authors

Dana M. Roque, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Eric R. Siegel, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Natalia Buza, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Stefania Bellone, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Dan-Arin Silasi, Division of Gynecologic Oncology, Mercy Clinic, St. Louis, MO, USA.
Gloria S. Huang, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Vaagn Andikyan, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Mitchell Clark, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Masoud Azodi, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Peter E. Schwartz, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Gautam G. Rao, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Jocelyn C. Reader, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Pei Hui, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Joan R. Tymon-Rosario, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Justin Harold, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Dennis Mauricio, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Burak Zeybek, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Gulden Menderes, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Gary Altwerger, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Elena Ratner, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Alessandro D. Santin, Smilow Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA. alessandro.santin@yale.edu.

Document Type

Article

Publication Title

British journal of cancer

Abstract

BACKGROUND: This multi-center RP2 study assessed activity/safety of ixabepilone + bevacizumab compared to ixabepilone in platinum-resistant/refractory ovarian/fallopian tube/primary peritoneal cancer. Additional objectives were to examine the role of prior bevacizumab and taxanes, and explore class III-ß-tubulin (TUBB3) as a predictive biomarker. METHODS: Participants were randomised to receive ixabepilone 20 mg/m days 1, 8, 15 with (IXA + BEV) or without (IXA) bevacizumab 10 mg/kg days 1, 15 every 28 days. Patients were stratified by prior BEV. The primary endpoint was PFS. OS, safety, and ORR served as secondary endpoints. RESULTS: Among 76 evaluable patients who received IXA + BEV (n = 39) compared to IXA (n = 37), the ORR was 33% (n = 13) versus 8% (n = 3)(P = 0.004), durable at 6 months in 37% (n = 14) and 3% (n = 1) (P < 0.001). BEV significantly improved PFS (median:5.5 vs 2.2 months, HR = 0.33, 95%CI 0.19-0.55, P < 0.001) and OS (median:10.0 vs 6.0 months, HR = 0.52, 95%CI 0.31-0.87, P = 0.006). Both regimens were well-tolerated. TUBB3 expression did not predict response. Subgroup analyses revealed minimal effect of prior BEV or taxane resistant/refractory status on response to IXA + BEV. CONCLUSIONS: IXA + BEV is a well-tolerated, effective combination for platinum/taxane-resistant ovarian cancer that extends PFS and likely OS relative to IXA monotherapy. Prior receipt of BEV should not preclude the use of IXA + BEV. TUBB3 is not a predictive biomarker. CLINICAL TRIAL REGISTRATION: NCT3093155.

First Page

1695

Last Page

1703

DOI

10.1038/s41416-022-01717-6

Publication Date

6-1-2022

Identifier

35149854 (pubmed); PMC8853032 (pmc); 10.1038/s41416-022-01717-6 (doi); 10.1038/s41416-022-01717-6 (pii)

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