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

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).

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.

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.

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