Frontline bevacizumab in ovarian clear cell versus high-grade serous ovarian cancer: survival outcomes and recurrence patterns in a real-world cohort

Ovarian clear cell carcinoma (OCCC) is associated with inferior survival compared to high-grade serous ovarian cancer (HGSOC), largely due to its relative chemoresistance and near-universal BRCA wild-type status. Whether frontline bevacizumab can mitigate this survival disadvantage in a real-world setting remains to be established. We retrospectively analyzed 128 patients with advanced ovarian cancer (OCCC, n = 42; HGSOC, n = 86) treated at China Medical University Hospital between January 2017 and December 2022. Treatment response, recurrence patterns, and survival outcomes were compared by histology and frontline bevacizumab use. Cox regression analyses were performed to identify prognostic factors for overall survival (OS) and progression-free survival (PFS). OCCC patients were significantly younger (51 vs. 58 years, p < 0.001), had lower CA-125 levels, and received frontline PARPi less frequently (4.8% vs. 24%, p = 0.007). The objective response rate was numerically higher with bevacizumab (90% vs. 78%, p = 0.078), and bevacizumab use was associated with a difference in recurrence pattern, including lower disseminated peritoneal recurrence (31% vs. 49%) and more pelvic/focal recurrence (15% vs. 2.2%; overall pattern comparison p = 0.025). Kaplan-Meier analysis demonstrated significantly better OS ( p = 0.0012) and PFS ( p = 0.01) with bevacizumab in the overall cohort, with a particularly pronounced OS benefit in HGSOC ( p = 0.0061). On univariate analysis, OCCC histology conferred significantly worse OS (HR 2.21, 95% CI 1.35–3.62, p = 0.002). On multivariate analysis, OCCC remained an independent predictor of worse OS (HR 3.03, 95% CI 1.71–5.34, p < 0.001) and PFS (HR 1.81, 95% CI 1.10–3.00, p = 0.02), while patients receiving frontline bevacizumab had longer OS (HR 0.52, 95% CI 0.30–0.90, p = 0.019). Although the effect of bevacizumab in OCCC subgroup did not reach statistical significance, the direction was consistent with that in HGSOC, and no significant interaction by histology was detected ( p = 0.505). In this real-world cohort, OCCC independently predicts inferior survival in advanced ovarian cancer. Frontline bevacizumab was associated with a numerically higher response rate, differences in recurrence pattern, and prolonged OS in the overall cohort. Given the observational design and limited subgroup sizes, these findings may support the consideration of frontline bevacizumab, particularly in OCCC where treatment options are limited, and warrant validation in prospective studies.