SynthesisBMC cancer2026
Safety and tolerability of PARP inhibitors in cancer patients: a network meta-analysis of randomized controlled trials.
Synthesis in BMC cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPoly(ADP-ribose) polymerase inhibitors (PARPi) for the treatment of homologous recombination (HR)-deficient cancers have revolutionized cancer treatment in recent years. Despite documented clinical benefits, the use of PARPi is associated with several adverse events (AEs) inducing poor prognosis. The aim of our study was to evaluate the safety and tolerability of different PARPi and PARPi-based therapies via a network meta-analysis based on randomized controlled trials (RCTs).
methodsWe systematically searched and assessed RCTs in PubMed, Embase, the Cochrane Library, and the ClinicalTrials.gov registry from inception to 1st March 2026. Studies assessed the safety of PARP inhibitors or PARPi-based therapies were included. The primary outcomes were serious AE and discontinuation of treatment due to AE. For statistical analysis, the fixed-effect or random-effect model was used, depending on the heterogeneity (I
resultsSixty-seven studies with 23,285 patients were included in the pooled safety analysis. All the 6 included PARPi were proven to have a higher risk of serious AE and AE-related discontinuation of treatment compared with placebo. Olaparib (OR, 0.21; 95% CI, 0.05-0.85) and pamiparib (OR, 0.14; 95% CI, 0.02-0.91) had significant lower risk from suffering serious AE compared with senaparib. Discontinuation of treatment did not differ significantly among the 6 included PARP inhibitors. The 5 PARPi-based therapies included in our study showed similar risk of serious AE. PARPi plus chemotherapy (OR, 2.56; 95% CI, 1.47-4.55) might increase significantly the risk of AE leading to discontinuation compared with PARPi alone. PARPi plus anti-angiogenic drug (OR, 3.66; 95% CI, 1.10-12.19) and PARPi plus chemotherapy (OR, 4.76; 95% CI, 1.54-14.29) had significant higher risk of AE-related discontinuation compared with PARPi plus ARSI.
conclusionIn our study, pamiparib demonstrates the most favorable safety profile among evaluated PARP inhibitors relatively, while senaparib might be associated with a higher incidence of AEs. PARPi plus anti-angiogenic drug or chemotherapy might cause the most occurrence of AEs relatively. Therefore, on the basis of balancing efficacy and safety, selecting optimal PARPi and formulating tailored combination therapy for individual patients is necessary.
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