Influence of Residual Disease on the Efficacy of PARP Inhibitors in Advanced Epithelial Ovarian Cancer: A Systematic Review and Meta Analysis

TL;DR

PARP inhibitors help prevent cancer recurrence in ovarian cancer patients, regardless of whether they had all the cancer tissue removed during surgery.

Contribution

This study is the first to show that PARP inhibitors are equally effective in preventing cancer progression in patients with or without residual disease after surgery.

Findings

PARP inhibitors significantly improved progression-free survival in patients with no residual disease (R0) and those with residual disease (R1/R2).

The treatment effect was similar between R0 and R1/R2 subgroups (p = 0.66).

Complete cytoreduction remains important for the best prognosis despite the effectiveness of PARP inhibitors.

Abstract

This systematic review and meta analysis evaluated six randomized controlled trials including 3629 patients to determine whether residual disease modifies the clinical benefit of PARP inhibitor maintenance therapy in advanced epithelial ovarian cancer. The analysis demonstrated that PARP inhibitors significantly improve progression-free survival in both patients with no gross residual disease (R0; hazard ratio 0.55, 95% confidence interval 0.44–0.68) and those with macroscopic residual disease (R1/R2; hazard ratio 0.51, 95% confidence interval 0.40–0.65). The treatment effect was similar between subgroups (p = 0.66). These findings indicate that PARP inhibitor maintenance therapy provides substantial benefit regardless of surgical outcome, supporting its use in all eligible patients after first-line platinum-based chemotherapy, while emphasizing that achieving complete cytoreduction remains vital for the best overall prognosis.

Objective: While PARP inhibitors (PARPi) improve progression-free survival (PFS) in advanced ovarian cancer, their efficacy across different surgical outcomes is unclear. We aimed to determine if the efficacy of PARPi maintenance therapy, as measured by PFS, is modified by postoperative residual disease (R0 vs. R1/R2) in newly diagnosed advanced epithelial ovarian cancer. Methods: A systematic review and trial-level meta analysis of randomized controlled trials published through July 2025 was conducted. The primary endpoint was pooled hazard ratio (HR) for PFS, with subgroup analyses based on residual disease (R0 vs. R1/R2), clinical risk (higher risk vs. lower risk), and timing of surgery (primary cytoreductive surgery vs. interval cytoreductive surgery). Results: Six randomized controlled trials involving 3629 patients were included in this meta analysis. PARPi maintenance significantly improved PFS in both patients with no gross residual disease (R0) (HR 0.55, 95% CI 0.44–0.68, I2 = 64.2%) and those with macroscopic residual disease (R1/R2) (HR 0.51, 95% CI 0.40–0.65, I2 = 56.0%). The treatment effect did not differ significantly between these subgroups (p = 0.66). A numerically greater benefit was observed in lower-risk populations (HR 0.40, 95% CI 0.29–0.55, I2 = 0.9%) compared to higher-risk populations (HR 0.51, 95% CI 0.36–0.73, I2 = 78.5%, p = 0.30). The benefit was maintained irrespective of surgical timing, with similar pooled HRs for patients undergoing primary (HR 0.56, 95% CI 0.42–0.74, I2 = 72.3%) versus interval (HR 0.54, 95% CI 0.45–0.66, I2 = 44.2%) cytoreductive surgery. Conclusions: PARP inhibitor maintenance therapy provides a significant PFS benefit regardless of residual disease status, supporting its use in all eligible patients. Complete cytoreduction, however, remains crucial, as it provides the best foundation for achieving optimal long-term outcomes and maximizing the benefits of maintenance therapy.

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