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Background <p>Poly(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).</p> Methods <p>We 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<sup>2</sup>).</p> Results <p>Sixty-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.</p> Conclusion <p>In 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.</p>

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Safety and tolerability of PARP inhibitors in cancer patients: a network meta-analysis of randomized controlled trials

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月10日

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  • Chenyu Wei,
  • Shujing Liu,
  • Jiexuan Hu,
  • Bangwei Cao,
  • Bing Liu

摘要

Background

Poly(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).

Methods

We 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 (I2).

Results

Sixty-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.

Conclusion

In 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.