KEY TAKEAWAYS
- The phase 2 trial aimed to investigate the efficacy and safety of weekly IXA ± biweekly BEV in chemo-resistant OC patients, with a focus on PFS and OS outcomes.
- The primary endpoint was to determine PFS and OS.
- Researchers observed that the combination of IXA+BEV shows activity in heavily pre-treated OC patients; further investigation is ongoing.
The microtubule-stabilizing agent ixabepilone (IXA) holds promise for retaining activity in paclitaxel-resistant disease.
Dana M. Roque and the team aimed to assess the efficacy and safety of weekly IXA ± biweekly bevacizumab (BEV) in chemotherapy-resistant ovarian cancers (OC). Meeting primary and secondary endpoints, the study demonstrated improved progression-free (PFS) and overall survival (OS) outcomes, alongside the absence of new safety concerns. Originally analyzed in November 2020, they now present updated data on objective response rates (ORR), PFS, and OS from a mature dataset, including additional subset analyses.
Researchers performed an inclusive analysis where patients with platinum-resistant/-refractory OC were stratified by prior BEV treatment and randomized to receive weekly IXA 20 mg/m2 days 1, 8, 15 ± biweekly BEV 10 mg/kg days 1, 15 of a 28-day cycle as part of a multi-site, prospective randomized trial. Survival was analyzed using the Kaplan-Meier method with one-sided log-rank tests and Cox regression.
Two-sided Fisher’s exact tests were used to compare response rates. Subgroup analyses were illustrated using Forest plots and analyzed with 2-tailed Wald tests. Patients were considered ‘taxane-resistant’ if they had demonstrated disease progression within 6 months of paclitaxel/docetaxel administration and ‘taxane-refractory’ if they progressed while receiving a taxane or demonstrated persistence of disease on end-of-treatment assessment that prompted initiation of a new line of therapy. All others were deemed ‘taxane-exposed.’
About 37 patients were randomized to receive monotherapy (IXA), while 39 patients received combination therapy (IXA + BEV). Both groups had a median of 4 prior lines of treatment and similar taxane-free intervals. By the final data cutoff, 75 PFS events and 70 deaths occurred among 76 participants. Approximately 59% of participants in the IXA group and 64% in the IXA+BEV group required a 20% dose reduction, with no significant impact on PFS or OS benefit even with two dose reductions.
The combination arm showed a higher ORR of 38.5% compared to 8.1% in the monotherapy arm (P=0.003). Median PFS was 5.5 months versus 2.2 months (HR 0.31, 90%CI 0.20-0.49, P<0.001), and median OS was 10.3 months versus 6.0 months (HR 0.56, 90%CI 0.38-0.84, P=0.02) for the IXA+BEV and IXA arms, respectively. The majority of patients in both arms were paclitaxel-refractory/-resistant (51% in IXA and 67% in IXA+BEV). Addition of BEV to IXA demonstrated benefits in PFS (HR 0.31, 90%CI 0.20-0.48, P<0.001) and OS (HR 0.59, 90%CI 0.39-0.88, P<0.03) even when adjusting for prior taxane response. Although there were no complete responses, 14 patients in the combination arm achieved a durable response (stable disease or partial response ≥ 6 months).
The study concluded that the combination of IXA+BEV exhibits activity in heavily pre-treated OC, providing substantial enhancements in ORR, PFS, and OS compared to IXA alone, irrespective of prior taxane response and even with dose reductions. Further molecular studies are necessary to identify predictors of durable response.
The study was sponsored by Yale University.
Source: https://sgo.planion.com/Web.User/AbstractDet?ACCOUNT=SGO&ABSID=498505&CONF=AM2024&CKEY=
Clinical Trial: https://clinicaltrials.gov/study/NCT03093155
Roque D M., Siegel E R., Bellone S, et al. (2024). “Randomized phase II trial of weekly ixabepilone with or without biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer: Updated survival and subgroup analyses.” Presented at SGO 2024.
