Cancer medicine · 2026
Survival Outcomes and Sensitivity of PARP Inhibitors in Platinum-Sensitive Ovarian Cancer: A Retrospective Study.
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Zhang Xiu, Wang Zhibin, Gu Yuhui, Fang Huihui, Wang Ying, Fang Chao, Wu Nayiyuan
Аннотация
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.
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.