PARP inhibitors as maintenance treatment in platinum sensitive recurrent ovarian cancer: an updated meta-analysis of randomized clinical trials according to BRCA mutational status
A partir d'une revue de la littérature, cette méta-analyse d'essais randomisés évalue l'efficacité, du point de vue de la survie sans progression, des inhibiteurs de PARP en traitement d'entretien chez des patientes atteintes d'un cancer de l'ovaire récidivant sensible aux sels de platine, en fonction du statut BRCA
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 5 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. Moreover, the studies that analysed the efficacy in HRD population reported a PFS improvement with PARPis 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. Further future investigations, testing the use of different PARPis as monotherapy, comparing them in terms of efficacy and toxicity and exploring their potential re-use would be useful.