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Clinical Studies

Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal 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/m2 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.

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Fig. 1
Fig. 2: Progression-free survival, overall survival, and subgroup analyses.

Data availability

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This study was presented on 03/25/2021 as an oral presentation at the late-breaking abstract session of the Annual Meeting of the Society of Gynecologic Oncology (#11570 https://157slyoyo4y17zpa538hczs1-wpengine.netdna-ssl.com/wp-content/uploads/2021/01/THURSDAY_2021-Virtual-Annual-Meeting-on-Womens-Cancer.pdf). We would like to thank RPharm-US for their industry support and Lisa Baker, Martha Luther, Kay Debski, Amy Nicoletti, Kerry DeBenedictis, Michele Hill, Nancy Tait, Paige Smith and Carolynn Harris for their invaluable technical support to the study.

Funding

Study drug was supplied by RPharm-US, LLC (Princeton, NJ)

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Collection and assembly of data: DMR, JR, GGR, JT-R, JH, DM, BZ, GM, GR, ER and ADS. Data analysis and interpretation: ES, NB, DMR, SB, PH, DAS, GH, VA, MC, MA, PES, GR, JR and ADS. Manuscript writing: DMR, ES and ADS. Final approval of the manuscript for publication: all authors. Accountable for all aspects of the work: all authors.

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Correspondence to Alessandro D. Santin.

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Roque, D.M., Siegel, E.R., Buza, N. et al. Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer. Br J Cancer 126, 1695–1703 (2022). https://doi.org/10.1038/s41416-022-01717-6

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  • DOI: https://doi.org/10.1038/s41416-022-01717-6

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