The Era of PARP inhibitors in ovarian cancer: “Class Action” or not? A systematic review and meta-analysis
Graphical abstract
Section snippets
Background
Among epithelial ovarian cancer (EOC) patients, women with genetic predisposition show an early onset of disease. Rare high penetrant mutations in BRCA1 and BRCA2 genes greatly increase lifetime risk and account for the majority of hereditary cases, 10%–15% of all cases. These women have a 40–60% lifetime risk of EOC (44% in BRCA1 families and 27% in BRCA2 families, respectively) (Mavaddat et al., 2012; Xu et al., 2017).
The gold standard first-line treatment is still based on the combination of
Aim
In order to assess by aggregate analysis the overall impact of PARPis in the management of EOC patients, we performed a systematic review of literature and we estimated this effect by a meta-analytic approach.
Study design
We performed a systematic review and meta-analysis of all published RCTs to evaluate the role of PARPis schedules compared to conventional therapies and wait-watchful approach in the management of EOC. In order to compare the different PARPis, we also performed an indirect-comparison meta-analysis in accordance with The Quality of Reporting of Meta-analyses (QUOROM) statements (Moher et al., 1999). The study includes therefore only prospective and RCTs on EOC in all treatment lines with PFS, as
Studies selection and characteristics
In Fig. 1, the PRISMA chart related to RCTs selection and search strategy is shown. In the time-frame covered by the present systematic review (2008–2018), 497 studies were reported as full papers or meeting abstracts, while 172 studies were initially excluded because reviews and/or for trial design. Subsequently, we examined in detail the remaining 325 trials. Among them, were excluded 76 and 46 trials respectively because selection criteria were not met and overlapping of other studies.
Discussion
This meta-analysis of 6 RCTs for a total of 1839 patients compares PARPi-based schedules to any other systemic conventional treatment and/or wait/watchful approach.
First of all, we confirmed the survival benefit for all PARPis individually and in the pooled analysis. In particular we evaluated a BRCAmt cohort (871 patients) with a pooled HR 0.25 (95%CI 0.21-0.31) and the BRCAwt cohort (836 patients) with a pooled HR 0.41 (95%CI 0.31-0.55), in term of PFS in recurrent platinum-sensitive EOC.
Author contributions
DC, NS, PT, and PT designed the study.
DC, NS, EI e TDG did the literature search.
DC, NS, TDG extracted data. DC realized the figures.
EI and TDG performed the tables.
All authors collected data.
DC, NS, PT, and, PT interpreted and analyzed the data, and wrote the manuscript.
All authors read and approved final version of the manuscript.
Disclosures
Acknowledgments
This work has been supported by PhD program of Magna Graecia University: “molecular oncology and translational and innovative medical and surgical techniques”.
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These authors contributed equally to this work.