Bevacizumab versus PARP-inhibitors in women with newly diagnosed ovarian cancer: a network meta-analysis

Abstract

Background: In women with newly diagnosed ovarian cancer, bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi) exhibit improved progression-free survival (PFS) when administered concurrent with chemotherapy and/or maintenance therapy, but no study has directly compared their effects. Therefore, this study aimed to compare the efficacy and safety of bevacizumab and PARPi in women with newly diagnosed ovarian cancer using a network meta-analysis.

Methods: PubMed, Medline, and Embase databases were searched, and five randomized trials assessing PFS in women with newly diagnosed ovarian cancer treated with either bevacizumab, PARPi, or placebo or no additional agent (controls) were identified. PFS was compared in the overall population with ovarian cancer, women with a BRCA1/2 mutation (BRCAm) and women with homologous-recombination deficiency (HRD). Adverse events (grade ≥ 3) were compared in all populations of the included studies.

Results: PARPi improved PFS significantly more than bevacizumab in women with a BRCAm (HR 0.47; 95% CI 0.36-0.60) and with HRD (HR 0.66; 95% CI 0.50-0.87). However, in the overall population with ovarian cancer, no significant difference in PFS was observed between women treated with PARPi and those treated with bevacizumab. PARPi exhibited the highest surface under the cumulative ranking probabilities value as the most effective treatment for PFS (PARPi vs. bevacizumab: 98% vs. 52% in the overall population with ovarian cancer; 100% vs. 50% in women with BRCAm; 100% vs. 50% in women with HRD). For adverse events, the risk of all treatments was similar. However, PARPi had a higher adverse risk than the control group (relative risk 2.14; 95% CI 1.40-3.26).

Conclusions: In women with newly diagnosed ovarian cancer, PARPi might be more effective in terms of PFS compared to bevacizumab. The risk of serious adverse events was similar for PARPi and bevacizumab.

Keywords: Adverse events; BRCA mutation; Bevacizumab; Homologous recombination deficiency; Ovarian cancer; Poly(ADP-ribose) polymerase inhibitors; Progression-free survival.

Fig. 1

Network plots of treatments for PFS and adverse events. A PFS in the overall population with ovarian cancer, B PFS of women with a BRCAm, C PFS of women with HRD, and D Adverse events in all populations. The size of the three nodes (treatments) increased with the number of studies included in the corresponding nodes, and lines connecting two nodes were thickened with larger number of studies comparing the two treatments [24]. BRCAm, BRCA1/2 mutation; HRD, homologous recombination deficiency

Fig. 2

League tables of treatments for PFS and adverse events. A PFS in the overall population with ovarian cancer, B PFS for women with BRCAm, C PFS for women with HRD, D Adverse events in all populations. Hazard ratio (HR) or relative risk (RR) of the upper left treatment (intervention) vs. lower right (comparator) was estimated. BRCAm, BRCA1/2 mutation; HRD, homologous recombination deficiency

Fig. 3

Forest plots of treatment for PFS and adverse events. A PFS in the overall population with ovarian cancer, B PFS for women with BRCAm, C PFS for women with HRD, D Adverse events in all populations. BRCAm, BRCA1/2 mutation; CI, confidence interval; HR, hazard ratio; HRD, homologous recombination deficiency