Integrating clinical-molecular data to predict PARP inhibitors efficacy in advanced ovarian cancer patients after interval cytoreductive surgery

Abstract

Objective

Selecting the maintenance strategy for advanced tubo-ovarian high-grade serous carcinoma (HGSC) is challenging. This study evaluates the correlation among chemotherapy response score (CRS), homologous recombination deficiency (HRD) status, and KELIM score; identifies predictors of Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) efficacy and stratifies recurrence risk in PARPi-treated population.

Methods

Median Progression-free Survival (mPFS) and hazard ratios (HRs) were retrospectively calculated in HGSC patients after neoadjuvant chemotherapy (3/4 cycles), interval cytoreductive surgery, and adjuvant treatment. Variables included HRD status, disease stage, KELIM, radiological response, residual tumor, and CRS at surgery. A risk-stratification model predicting PARPi efficacy was developed.

Results

Among overall population (N = 373), 66.9 % of CRS3 patients reached favorable KELIM, 17.3 % had complete radiological response, and 97.8 % achieved complete surgery, with higher frequencies than CRS1/2 (p < 0.001). Univariate analysis of PFS on PARPi (N = 210) showed favorable covariates: CRS3 (HR 2.37, 95 % CI 1.39–4.04 and HR 1.59, 95 % CI 1.03–2.47 vs CRS1 and CRS2), BRCA mutation (HR 3.41 95 % CI 2.15–5.39 and HR 2.00 95 % CI 1.13–3.56 vs BRCAwt-HRDneg and -HRDpos) and continuum KELIM (HR 0.66, 95 % CI 0.45–0.96). At multivariate, CRS3 and BRCA mutation were confirmed significant. Combining HRD status, CRS, and KELIM four prognostic groups with different PARPi efficacy were identified (mPFS 38 vs 26 vs 18 vs 6 months for Low, Intermediate, High-Intermediate, and High-risk groups).

Conclusions

CRS is a prognostic factor in PARPi-treated population as a PARPi efficacy surrogate. Integrating HRD status, CRS, and KELIM allows patients risk stratification and tailored maintenance. These results should be considered hypothesis-generating.