Abstract
Introduction: Targeted agents such as bevacizumab (BEV) or poly (ADP-ribose) polymerase inhibitors (PARPi) which have been added as concomitant or maintenance therapies have been shown to improve progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer (PS rOC). In the absence of direct comparison, we performed a network meta-analysis considering BRCA genes status. Methods: We searched PubMed, EMBASE, and MEDLINE for trials involving patients with PS rOC treated with BEV or PARPi. Different comparisons were performed for patients included in the PARPi trials, according to BRCA genes status as follows: all comers (AC) population, BRCA 1/2 mutated (BRCAm), and BRCA wild type patients (BRCAwt). Results: In the overall population, PARPi prolonged PFS with respect to BEV (hazard ratio (HR) = 0.70, 95% CI 0.54–0.91). In the BRCA mutated carriers, the PFS improvement in favor of PARPi appeared to be higher (HR = 0.46, 95% CI 0.36–0.59) while in BRCAwt patients the superiority of PARPi over BEV failed to reach a statistically significance level (HR = 0.87, 95% CI 0.63–1.20); however, according to the SUCRA analysis, PARPi had the highest probability of being ranked as the most effective therapy (90% and 60%, for PARPi and BEV, respectively). Conclusions: PARPi performed better as compared with BEV in terms of PFS for the treatment of PS rOC, especially in BRCAm patients who had not previously received PARPi.
Highlights
Targeted agents such as bevacizumab (BEV) or poly (ADP-ribose) polymerase inhibitors (PARPi) which have been added as concomitant or maintenance therapies have been shown to improve progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer (PS rOC)
As a matter of fact, results from three phase III trials have shown an improvement in progression-free survival (PFS) with the addition of bevacizumab in association with a platinum-based chemotherapy, and as maintenance therapy, as compared with chemotherapy alone, a benefit observed in patients previously exposed to first-line bevacizumab-containing therapy [4,5,6]
If the presence of BRCA mutation is considered to be a predictive factor for PARPi benefit, currently, for the vast majority of patients with a BRCA wild type (BRCAwt) status, there are no predictive biomarkers for PARPi or for bevacizumab that could guide the clinicians’ choice between the two target therapies [15]
Summary
Targeted agents such as bevacizumab (BEV) or poly (ADP-ribose) polymerase inhibitors (PARPi) which have been added as concomitant or maintenance therapies have been shown to improve progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer (PS rOC). The therapeutic armamentarium for platinum-sensitive recurrent EOC has taken a step forward by approving three drugs belonging to the PARPi class (i.e., olaparib, niraparib, and rucaparib) These drugs have been tested in phase II and phase III placebo-controlled trials as maintenance therapy after partial or complete response to a platinum-based treatment, showing a benefit to progression-free survival in the overall population of recurrent EOC patients, especially in those with a germline (gBRCA) or somatic (sBRCA) mutation in the BRCA 1/2 genes [7,8,9,10,11,12]. We performed a network meta-analysis (NMA) to evaluate the differences in terms of efficacy between bevacizumab and PARPi therapies for women with platinum-sensitive recurrent EOC, according to BRCA genes status
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