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.

Trial registration: ClinicalTrials.gov NCT03093155.

Fig. 1

Consolidated Standards of Reporting Trials (CONSORT) diagram shows progress through randomization.

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

a Progression-free survival: use of bevacizumab (BEV) with ixabepilone (IXA) significantly extended progression-free survival (5.5 vs 2.2 months, HR 0.33, 95% CI 0.19–0.55, p < 0.001) compared to IXA alone. b Overall Survival: overall survival was significantly longer in patients who received BEV in conjunction wiht IXA (10.0 vs 6.0 months, HR 0.52, 95% CI 0.31–0.87, p < 0.006). c Hazard ratios for progression-free survival versus treatment arm by subgroup: progression-free survival hazard radios were similar between arms among patients with prior BEV exposure (HR 0.36, 95% CI: 0.19–0.72, p = 0.003) and those who were BEV-naive (HR 0.27, 95%CI: 0.12–0.62, p = 0.002). Stratification by pre-treatment status, age, histology, and performance status are also shown. Error bars denote 95% confidence intervals (CI). d Hazard ratios for overall survival versus treatment arm by subgroup: similar hazard ratios for overall survival were observed between arms among patients with prior BEV exposure (HR 0.50, 95%: 0.25–1.02, p = 0.058) and those who were BEV-naive (HR 0.54, 95% CI: 0.24–1.22, p = 0.14). Stratification by pre-treatment status, age, histology, and performance status are also shown. Error bars denote 95% CI.