Poly (ADP-ribose) polymerase inhibitors (PARPi) for treating advanced epithelial ovarian cancer

RATIONALE: Ovarian cancer is the eighth most common cancer in women worldwide. Epithelial ovarian cancer (EOC) is the most common type; three-quarters of cases present with advanced disease (stage III or IV). Treatment consists of combinations of surgery and chemotherapy. Although initial responses to chemotherapy are good, most women with advanced disease relapse. Poly (ADP-ribose) polymerase inhibitors (PARPi) prevent cancer cells from repairing DNA damage, especially in those with breast cancer susceptibility gene (BRCA) mutations (BRCA-mutant), thereby offering a different mechanism of action for anticancer treatment compared to conventional chemotherapy. This is an update to a review first published in 2010 and previously updated in 2015 and 2022. OBJECTIVES: To assess the benefits and harms of poly (ADP-ribose) polymerase inhibitors (PARPi) versus placebo or other anti-cancer treatments for women with newly diagnosed or recurrent epithelial ovarian cancer (EOC). SEARCH METHODS: We identified randomised controlled trials (RCTs) by searching the Cochrane Central Register of Controlled Trials MEDLINE, and Embase up to 2 December 2025. ELIGIBILITY CRITERIA: We included trials randomising women with EOC to PARPi versus no treatment/placebo, PARPi versus conventional chemotherapy, or PARPi together with conventional chemotherapy versus conventional chemotherapy alone. OUTCOMES: We extracted data on overall survival (OS) and progression-free survival (PFS), severe adverse events, and quality of life. RISK OF BIAS: We used the Cochrane tool RoB 1 to assess the risk of bias in the included studies. SYNTHESIS METHODS: We conducted meta-analyses using the random-effects model to calculate hazard ratios (HR), risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI). We assessed the certainty of evidence using GRADE. INCLUDED STUDIES: We identified 10 new studies. We included a total of 24 studies (8961 participants) in this 2026 version of the review: eight (4801 participants) with newly-diagnosed, advanced EOC and 16 (4160 participants) with recurrent EOC. RESULTS: The studies evaluated different PARPi against various comparators. Below we present four key comparisons. Most participants had BRCA mutations, either in their tumour (sBRCA-mutant) and/or germline (gBRCA-mutant), or homologous recombination deficiencies (HRD) in their tumours. Newly diagnosed EOC PARPi versus placebo maintenance after chemotherapy PARPi maintenance treatment after chemotherapy may increase overall survival (OS) (HR 0.80, 95% CI 0.58 to 1.10; I² = 70%; 5 studies, 2852 participants; low-certainty evidence), but data are confounded by subsequent treatments, including increased use of PARPi in those in the placebo arms following relapse. PARPi maintenance results in a large improvement in progression-free survival (PFS), irrespective of PARPi type (HR 0.51, 95% CI 0.41 to 0.64; I² = 77%; 7 studies, 3618 participants; high-certainty evidence). PARPi maintenance may result in a slight reduction in quality of life (MD -1.06, 95% CI -3.52 to 1.40; I² = 92%; 3 studies, 1505 participants; low-certainty evidence), but this reduction may not be clinically meaningful. PARPi maintenance results in a large increase in the risk of any severe adverse event (grade 3 or higher; RR 2.66, 95% CI 1.66 to 4.27; I² = 91%; 7 studies, 3648 participants; high-certainty evidence). Recurrent, platinum-sensitive EOC PARPi versus placebo maintenance after chemotherapy PARPi maintenance probably increases OS slightly (HR 0.88, 95% CI 0.75 to 1.04; I² = 26%; 5 studies, 1797 participants; moderate-certainty evidence) and results in a large increase in PFS compared to placebo (HR 0.34, 95% CI 0.28 to 0.40; I² = 24%; 6 studies, 2194 participants; high-certainty evidence). PARPi maintenance probably results in little to no difference in quality of life measured using the European Quality of Life 5-dimensions questionnaire Health Utility Index score (MD 0.02, 95% CI -0.01 to 0.05; 1 study, 339 participants; moderate-certainty evidence) or the TOI score (FACT-O questionnaire; MD -0.03, 95% CI -2.16 to 2.10; 1 study, 279 participants; moderate-certainty evidence). However, there is probably a substantially increased risk of any severe adverse event (grade 3 or higher) (RR 3.03, 95% CI 2.11 to 4.36; I² = 61%; 6 studies, 2181 participants; moderate-certainty evidence). PARPi monotherapy versus chemotherapy PARPi monotherapy probably results in little to no difference in OS compared with chemotherapy (HR 1.14, 95% CI 0.95 to 1.37; I² = 0%; 4 studies, 832 participants; moderate-certainty evidence); we are very uncertain about the effect on PFS (HR 0.87, 95% CI 0.62 to 1.23; I² = 58%; 5 studies, 969 participants; very low-certainty evidence). PARPi monotherapy may result in little to no difference in quality of life compared with chemotherapy (FACT-O; MD 1.20, 95% CI -1.76 to 4.16; 1 study, 229 participants; low-certainty evidence; global EORTC QLQ-C30 score; MD 0.20, 95% CI -1.79 to 2.19; 1 study, 291 participants; very low-certainty evidence), but may increase the risk of any severe adverse event (grade 3 or higher) (RR 1.30, 95% CI 0.92 to 1.83; I² = 70%; 2 studies, 599 participants; low-certainty evidence). Recurrent, platinum-resistant EOC PARPi monotherapy versus chemotherapy Compared with chemotherapy, PARPi monotherapy reduces OS (HR 1.36, 95% CI 1.12 to 1.65; I² = 54%; 3 studies, 371 participants; high-certainty evidence) and may have little to no effect on PFS (HR 1.07, 95% CI 0.90 to 1.27; I² = 0%; 3 studies, 371 participants; low-certainty evidence). No quality of life data were available, but PARPi may result in little to no difference in the risk of any severe adverse event (grade 3 or higher) compared to chemotherapy (RR 1.16, 95% CI 0.79 to 1.70; 1 study, 100 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: PARPi maintenance treatment in women with first-line and platinum-sensitive recurrent disease improves progression-free survival (PFS) considerably, although it has less effect on overall survival (OS) and the OS results are less certain. PARPi maintenance increases severe adverse events, at times when women would otherwise not be on treatment, although quality of life may not be greatly impacted. The use of PARPi in other contexts did not lead to improved outcomes, especially in platinum-resistant recurrent disease. Adverse events and patient-reported outcomes were often poorly reported, which is a concern as this information is crucial for patient decision-making. FUNDING: No dedicated funding REGISTRATION: Protocol (2009) DOI: 10.1002/14651858.CD007929 Review (2010) DOI:10.1002/14651858.CD007929.pub2 Update (2015) DOI: 10.1002/14651858.CD007929.pub3 Update (2022) DOI: 10.1002/14651858.CD007929.pub4.