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Parp inhibitors as maintenance treatment in platinum sensitive recurrent ovarian cancer: An updated meta-analysis of randomized clinical trials according to BRCA mutational status

Published:October 09, 2019DOI:https://doi.org/10.1016/j.ctrv.2019.101909

      Highlights

      • New therapeutic strategies in OC have led to a patient-tailored medicine.
      • PARPis, as new agents, have improved the maintenance-therapy landscape in ROC.
      • The effectiveness of PARPis in BRCA-mutated platinum sensitive ROC is confirmed.
      • PARPis are effective in BRCA wild type and whole population, to a lesser extent.
      • PARPis are effective regardless of BRCA mutational status.

      Abstract

      Objective

      This meta-analysis investigated the effectiveness of PARP inhibitors (PARPis) as maintenance treatment in platinum sensitive recurrent ovarian cancer (ROC), stratifying results based on BRCA mutational status into five different categories: whole population, germ-line BRCA mutated patients, somatic BRCA mutated patients, HRD patients and wild type population.

      Methods

      PubMed, Medline, Scopus, EMBASE and clinicaltrials.gov, as well as meeting proceedings were searched for eligible studies that described RCTs testing the efficacy of PARPis as maintenance treatment in platinum sensitive ROC. Data were extracted independently and analysed using RevMan statistical software version 5.3. Primary end-point was progression free survival (PFS).

      Results

      The analysis confirmed the positive effect of PARPis in patients with platinum sensitive ROC in case of germinal or somatic BRCA mutations. Specifically, HR for PFS was 0.26, 95% CI 0.21–0.31, p < 0.00001 for the mutation of BRCA gene and 0.24, 95%, CI 0.12–0.48, p < 0.0001 for the somatic alteration. In addition, in the HRD population, studies that analysed the efficacy of PARPis  reported a PFS improvement with HR 0.34, 95% CI 0.26–0.43, p < 0.00001. Finally, our analysis confirms the role of these drugs in prolonging PFS in the whole population with HR 0.36, 95% CI 0.32–0.42, p < 0.00001, although to a lesser extent, with a significant improvement even in wild type cancers with HR 0.49, 95%, CI 0.41–0.59, p < 0.00001).

      Conclusions

      PARPis are effective regardless of BRCA mutational status. Future investigations are necessary to explore the use of different PARPis as monotherapy, comparing them among each other in terms of efficacy and toxicity, and exploring their potential re-use.

      Keywords

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