Impact of prior olaparib use on subsequent platinum-based therapy in recurrent ovarian cancer.

Abstract

Objective: Epithelial ovarian cancer (EOC) has the highest mortality among gynecologic malignancies, with frequent recurrences despite initial responsiveness to platinum. Poly(ADP-ribose) polymerase (PARP) inhibitors, such as olaparib, have improved progression-free survival in BRCA-mutated and homologous recombination-deficient EOC. However, emerging evidence suggests that prior exposure to PARP inhibitors may reduce the efficacy of subsequent platinum-based chemotherapy, raising concerns about treatment sequencing. To evaluate whether prior olaparib use affects the sensitivity to subsequent platinum-based chemotherapy in patients with recurrent platinum-sensitive ovarian cancer, and to explore potential predictive biomarkers such as the neutrophil-to-lymphocyte ratio (NLR).

Methods: We retrospectively analyzed 46 patients with recurrent ovarian cancer treated between 2008 and 2024. Patients were divided into an olaparib group (n=22) and a control group (n=24) without prior PARP inhibitor use. The primary endpoint was the difference between progression-free survival interval after second- and first-line therapy (PFS2 and PFS1). Secondary endpoints included time to first subsequent therapy (TFST)-time to second subsequent therapy (TSST) and correlations of NLR and CA125 with PFS2-PFS1.

Results: The olaparib group had a significantly shorter PFS2-PFS1 (mean 6.40 vs. 11.17 months, p=0.023). TFST-TSST was shorter in the olaparib group (7.73 vs. 11.46 months) but not statistically significant (p=0.156). NLR was inversely correlated with PFS2-PFS1, and was strongest at 4 months (r=-0.515) and 5 months (r=-0.624) post-treatment in the olaparib and control groups, respectively. CA125 showed no significant correlation.

Conclusion: Olaparib exposure may impair later chemotherapy efficacy. Careful treatment sequencing and biomarker development are warranted to optimize outcomes.