1. Parp inhibitors as maintenance treatment in platinum sensitive recurrent ovarian cancer: An updated meta-analysis of randomized clinical trials according to BRCA mutational status
- Author
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Carolina Maria Sassu, Erlisa Bardhi, Anna Di Pinto, Maria Cristina Petrella, Elena Biagioli, Pierluigi Benedetti Panici, Innocenza Palaia, Ludovico Muzii, Nicoletta Colombo, Federica Tomao, Tomao, F, Bardhi, E, Di Pinto, A, Sassu, C, Biagioli, E, Petrella, M, Palaia, I, Muzii, L, Colombo, N, and Panici, P
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,endocrine system diseases ,Population ,Genes, BRCA2 ,Genes, BRCA1 ,Gene mutation ,Maintenance therapy in ovarian cancer ,Poly(ADP-ribose) Polymerase Inhibitors ,Olaparib ,Maintenance Chemotherapy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Maintenance therapy ,Internal medicine ,Platinum sensitive ovarian cancer ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Progression-free survival ,education ,Rucaparib ,Germ-Line Mutation ,Randomized Controlled Trials as Topic ,Ovarian Neoplasms ,education.field_of_study ,business.industry ,BRCA mutation ,General Medicine ,female genital diseases and pregnancy complications ,030104 developmental biology ,PARP inhibitor ,chemistry ,030220 oncology & carcinogenesis ,Meta-analysis ,HRD ,Female ,Recurrent ovarian cancer ,Neoplasm Recurrence, Local ,business - 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.
- Published
- 2019