The Era of PARP inhibitors in ovarian cancer: "Class Action" or not? A systematic review and meta-analysis. (November 2018)

• Record Type: Journal Article
• Authors: Staropoli, Nicoletta; Ciliberto, Domenico; Del Giudice, Teresa; Iuliano, Eleonora; Cucè, Maria; Grillone, Francesco; Salvino, Angela; Barbieri, Vito; Russo, Antonio; Tassone, Pierfrancesco; Tagliaferri, Pierosandro
• Is Part Of: Critical reviews in oncology/hematology. Volume 131(2018)
• Page Start: 83
• Page End: 89
• Publication Date: 2018-11
• Subjects: Ovarian cancer -- PARP inhibitors -- Maintenance therapy -- Randomized clinical trials -- Meta-analysis; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2018.08.011
• Languages: English
• ISSNs: 1040-8428

Abstract

Graphical abstract: Abstract: Introduction: Carboplatin is the milestone of epithelial ovarian cancer (EOC) treatment, thus response to platinum is the major prognostic factor. Among platinum-sensitive patients, 40% carry a germline or somatic BRCA1/2 mutation. In this scenario a new class of drugs, the PARP inhibitors (PARPis), produced a significant improvement in long-term disease control. In order to make an aggregate evaluation of the impact of these agents, we performed a systematic review and meta-analysis. Patients and Methods: Clinical trials were selected by searching "Pubmed" database and abstracts from major cancer meetings. We considered the January 2008 - April 2018 time frame. Progression free survival (PFS) was the primary end-point, toxicities were secondary end-points. Hazard ratios (HRs) of PFS, with confidence intervals, and risk ratios of grade 3–4 toxicity rates, were extracted from retrieved studies and included in the current analysis. Meta-analysis was carried out by the fixed and random effect models. We conducted this meta-analysis to also compare indirectly the efficacy of different PARPis in EOC patients. Results: Five randomized trials for a total of 1839 patients were selected and included in the final analysis. In particular, we evaluated a BRCA-mutant cohort (871 patients) with a pooled HR 0.25 (95%CI 0.21-0.31) and the BRCA-wild type cohort (836 patients) with a pooled HR 0.41 (95%CI 0.31-0.55), respectively. Regarding safety profile, no significant differences were detected in all grade toxicities, however, taking into account 3–4 grade toxicities and SAEs (severe adverse events), we show that rucaparib-treated patients reported major abdominal pain events, while niraparib-treated patients were associated with the highest percentage of haematological toxicities, hypothesizing a drug effect for the safety analysis. In the indirect comparisons, significant differences were not detected on PFS for the different agents. Conclusions: We confirm a significant benefit in survival outcome of PARPis for EOC patients with a "class effect" on the bases of narrow CI and indirect comparisons in the different groups. Therefore, we underline that this strategy is of special value in BRCA-mutated patients because genetic testing allows best patient selection for all PARPis with the added value of individualized prevention in familiars.