Bevacizumab rechallenge in platinum-resistant ovarian cancer: Evidence from a propensity score–matched analysis.

Abstract

5607 Background: Bevacizumab is approved for the treatment of ovarian carcinoma across multiple disease settings, from first-line therapy to late platinum-resistant recurrences (PROC). The greatest relative benefit of bevacizumab has been observed in the platinum-resistant setting. While evidence supports bevacizumab rechallenge in the first platinum-sensitive recurrence, no randomized trial has demonstrated a benefit of bevacizumab rechallenge in PROC. Methods: We conducted a retrospective cohort study including patients with PROC treated with chemotherapy with or without bevacizumab. Patients were matched using propensity score matching based on histology (HGSC vs others), chemotherapy backbone, line of platinum-resistant treatment, age, BRCA pathogenic variant status, and prior bevacizumab exposure. Nearest-neighbor matching with a 1:2 ratio (bevacizumab:non-bevacizumab) and a caliper of 0.2 was applied. Balance between groups was assessed using standardized mean differences. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier methods and compared using log-rank tests. Hazard ratios (HRs) were estimated using Cox proportional hazards models with robust variance accounting for matching. Subgroup analyses were performed according to prior bevacizumab exposure, and treatment–exposure interaction was formally tested. Results: A total of 149 patients with PROC were included. Baseline clinicopathologic characteristics were well balanced between treatment groups. In the overall matched cohort, bevacizumab use was associated with significantly improved PFS compared with chemotherapy alone (median PFS 7.79 vs 4.37 months; HR 0.49, 95% CI 0.36–0.68; p<0.001), as well as improved OS (median OS 23.06 vs 10.45 months; HR 0.47, 95% CI 0.34–0.66; p<0.001). In bevacizumab-naïve patients, bevacizumab remained significantly associated with longer PFS (median 7.79 vs 4.04 months; HR 0.47, 95% CI 0.33–0.68; p<0.001) and OS (median 23.06 vs 10.05 months; HR 0.46, 95% CI 0.32–0.67; p<0.001). Among patients previously exposed to bevacizumab, re-exposure was associated with numerically longer PFS (median 8.49 vs 4.89 months; HR 0.61, 95% CI 0.31–1.20; p=0.15) and OS (median 21.29 vs 10.45 months; HR 0.54, 95% CI 0.26–1.11; p=0.09), although these differences did not reach statistical significance. There was no statistically significant interaction between prior bevacizumab exposure and treatment effect for PFS (p for interaction = 0.60). Conclusions: The addition of bevacizumab to chemotherapy is associated with significant benefit in bevacizumab-naïve patients with PROC. In patients previously exposed to bevacizumab, re-exposure was not associated with a statistically significant improvement in outcomes, underscoring ongoing uncertainty regarding the role of bevacizumab rechallenge in this setting.