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. 2024 Jun 20;2(1):43.
doi: 10.1038/s44276-024-00067-5.

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  1 , Eric R Siegel  2 , Natalia Buza  3 , Stefania Bellone  4 , Gloria S Huang  4 , Gary Altwerger  4 , Vaagn Andikyan  4 , Mitchell Clark  4 , Masoud Azodi  4 , Peter E Schwartz  4 , Gautam G Rao  1 , Elena Ratner  3 , Alessandro D Santin  5
Affiliations

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 et al. BJC Rep. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
CONSORT (Consolidated Standards of Reporting Trials) diagram.
Fig. 2
Fig. 2
Swimmer’s plot of responses among 39 patients who received ixabepilone and bevacizumab.
Fig. 3
Fig. 3
Progression-free (top) and overall (bottom) survival among patients in the setting of ixabepilone dose reductions (left, none; middle, one dose reduction, right, two dose reductions).
Fig. 4
Fig. 4
Progression-free (top) and overall (bottom) survival among patients in 23 patients who received prior weekly paclitaxel.
See this image and copyright information in PMC

References

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