Efficacy of chemotherapy after PARP inhibitor progression in ovarian cancer: A large real-world cohort.

e17592 Background: PARP inhibitors (PARPi) have revolutionized the treatment of ovarian cancer in the maintenance setting. However, accumulating evidence suggests limited efficacy of subsequent therapies following disease progression on PARPi. The aim of this study was to evaluate the clinical activity of chemotherapy after PARPi progression and to explore potential predictive clinical or molecular biomarkers. Methods: We retrospectively reviewed the medical records of ovarian cancer patients treated with PARPi as maintenance therapy following platinum-based chemotherapy for newly diagnosed or recurrent disease at Alexandra Hospital, Greece. Clinicopathological characteristics, molecular data, treatment details, and survival outcomes were collected. Results: A total of 255 patients were included. Median age was 59.9 years (IQR 50.9–67.8). Most patients had serous histology (247/255, 96.9%), ECOG performance status 0–1 at diagnosis (224/255, 87.8%), and advanced-stage disease. Primary debulking surgery was performed in 145 patients (56.9%), and 92 patients (36.1%) harbored BRCA1/2 mutations. PARPi was administered as first-line maintenance in 174 patients (67.4%), with olaparib being the most frequently used agent (195 patients, 76.5%). Median follow-up was 37.9 months. Median progression-free survival (PFS) on PARPi was 15.8 months (95% CI 9.8–21.8). Disease progression occurred in 164 patients, predominantly during PARPi treatment (142 patients, 86.6%), while 22 patients (13.4%) progressed after completion of PARPi maintenance. Median PFS with subsequent chemotherapy was 5.4 months (95% CI 4.5–6.3). Post-PARPi PFS was longer in patients with a platinum-free interval ≥12 months (6.2 vs 5.0 months, p=0.043) and in those progressing after PARPi completion compared with progression during PARPi treatment (11.6 vs 5.1 months, p=0.050). No significant association was observed with line of therapy or BRCA1/2 mutation status. Overall response rate was 23.9%, and disease control rate was 64.8%. Median overall survival following PARPi progression was 22.0 months (95% CI 18.5–25.5), independent of clinical or molecular characteristics. Conclusions: In this large real-world cohort, chemotherapy following progression on PARP inhibitor maintenance demonstrated limited clinical benefit. Modest improvements were observed in patients with longer platinum-free intervals or progression after PARPi completion, while outcomes were not influenced by BRCA mutation status or treatment line. These findings highlight a substantial unmet need and support the urgent development of novel therapeutic strategies for patients progressing after PARPi therapy.