Could chemotherapy response score act as a surrogate marker of response to PARP inhibitor maintenance treatment in patients with advanced ovarian cancer?

OBJECTIVE: Poly-ADP-ribose-polymerase inhibitors (PARPi) are often used as maintenance therapy in advanced epithelial ovarian cancer following primary treatment. The objective of this study was to evaluate whether the degree of response to chemotherapy (measured by the pathology-based Chemotherapy Response Score (CRS) at interval debulking surgery) is associated with a survival benefit from PARPi maintenance. METHODS: Retrospective cohort study of patients with high-grade epithelial ovarian cancer who received neoadjuvant chemotherapy followed by interval debulking surgery between January 2016 and September 2022 at one high-volume academic center. Demographic, clinical, and treatment data were retrieved from hospital records. RESULTS: Of 213 eligible patients, CRS was reported for 169. 47 patients received PARPi maintenance, with dose reductions required in 53.2%. Baseline characteristics were similar between CRS 1 (minimal/no response) and CRS 2-3 (moderate/marked response) groups. CRS 1 was associated with lower rates of complete cytoreduction (44.1% vs 69.3%, p < 0.0001) and inferior PFS, irrespective of PARPi maintenance (p = 0.017). Among patients with CRS 2-3, PARPi maintenance improved PFS (20 vs 15 months, p = 0.029), whereas no benefit was observed in CRS 1 patients (p = 0.27). Multivariable analysis adjusting for BRCA status and surgical outcome yielded similar results. CONCLUSIONS: In patients demonstrating substantial response to neoadjuvant chemotherapy (CRS 2-3), PARPi maintenance was associated with improved PFS, whereas no benefit was observed for CRS 1. The score may aid counseling regarding PARPi initiation, particularly in BRCA-wildtype patients or where homologous recombination deficiency (HRD) testing access is limited.