Survival Outcomes and Sensitivity of PARP Inhibitors in Platinum-Sensitive Ovarian Cancer: A Retrospective Study.

BACKGROUND

Poly (ADP-ribose) polymerase inhibitors (PARPi) have reshaped the maintenance treatment of ovarian cancer. However, a significant proportion of patients exhibit primary resistance, highlighting the need for real-world efficacy data and predictive biomarkers, especially in underrepresented populations.

METHODS

This retrospective study analyzed 152 Chinese patients with platinum-sensitive ovarian cancer who received maintenance therapy with olaparib or niraparib, either in the first-line (n = 71) or second-/later-line (n = 81) setting. Progression-free survival (PFS), progression-free interval (PFI), and overall survival (OS) were estimated using the Kaplan-Meier method. An objective, data-driven definition of PARPi sensitivity/resistance was established using receiver operating characteristic (ROC) curve analysis of PFS. Exploratory transcriptomic sequencing and immunohistochemistry (IHC) were performed on a subset of tumors to identify molecular correlates of response.

RESULTS

In the first-line maintenance cohort, median PFS (mPFS) was 54.35 months and median PFI (mPFI) was 49.57 months. In the second-/later-line group, mPFS was 42.53 months and mPFI was 34.87 months. Based on ROC-defined cutoffs (PFS of 11.6 and 11.8 months, respectively), 22.5% and 24.7% of patients were classified as PARPi-resistance in the first- and second-/later-line groups. Patients classified as sensitive consistently demonstrated superior PFS, PFI, and OS. Exploratory molecular analysis implicated the ferroptosis and HIF-1 signaling pathways in the response mechanism, and IHC validation confirmed differential protein expression of TFRC (lower in resistance tumors) and PRNP (higher in resistance tumors).

CONCLUSIONS

PARPi maintenance therapy demonstrates substantial clinical benefit in real-world Chinese patients with ovarian cancer. However, over 20% exhibit primary resistance. TFRC and PRNP represent promising biomarkers for predicting PARPi sensitivity and warrant further validation.