Real-world outcomes of olaparib with versus without bevacizumab in bevacizumab-naïve BRCA1/2-mutated ovarian cancer.

5574 Background: For patients with BRCA1/2-mutated epithelial ovarian, fallopian tube, or primary peritoneal cancer who complete primary platinum-based therapy, maintenance strategies differ based on prior bevacizumab (Bev) exposure. Patients who received Bev during frontline platinum therapy may receive Bev plus olaparib, whereas those without prior Bev exposure are generally treated with olaparib alone. No real-world evidence has evaluated outcomes of adding Bev to olaparib in patients who did not receive Bev during initial treatment. Using a large multi-institutional electronic health record dataset, we compared survival outcomes between olaparib monotherapy and olaparib–Bev combination therapy in this population. Methods: Adult patients from 2015-2024 with a diagnosis of ovarian, fallopian tube, or peritoneal cancer who received platinum chemotherapy followed by olaparib were first identified. Patients were then categorized based on bevacizumab exposure around the time of olaparib initiation (-1 to +3 months). This group was compared to patients who did not received Bev at any time. The index date was defined as 3 months after olaparib initiation to align treatment timing and minimize immortal time bias and propensity score matching was performed on age, race, metastatic sites, comorbidities, and prior treatments. Follow-up was then truncated at 3-years. Results: Before matching, 111 patients received Bev around the time of olaparib and 1,461 did not. After matching, 110 patients remained in each group with balanced characteristics. Three-year overall survival was significantly lower in the Bev group compared with the no-Bev group (52% vs 73%; HR 2.28, 95% CI 1.4–3.8; p=0.001). Treatment switching also occurred more often in the Bev group (54% vs 22%, p < 0.0001), with a median time to switching of 16.7 months; the no-Bev group did not reach median time. Conclusions: In real-world clinical practice, the addition of bevacizumab to olaparib in patients without prior bevacizumab exposure was associated with worse survival outcomes and earlier treatment switching. These findings may reflect the selection of patients with more aggressive or treatment-resistant disease for combination therapy, or they may suggest that intensifying therapy in this setting does not confer added benefit. Prospective, controlled studies are needed to clarify the underlying reasons for these observations and to better define which patients, if any, derive benefit from this treatment approach.