Article Text
Abstract
Background Several studies explored the clinical benefit of maintenance PARP inhibitors (PARPI) and antiangiogenic agents (AA) in advanced ovarian cancer (aOC) with varied results. We conducted this analysis to expand our knowledge of the relative adverse-events (AE) and efficacy of firstline maintenance PARPI and AA in aOC.
Methods A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of aOC; firstline maintenance treatment with Olaparib (O), Niraparib (NR), Veliparib (V), Bevacizumab (B), Pazopanib (P), Nintedanib (NN), and control (C); and phase 3 randomized studies reporting progression, death, and AE. A frequentists and Bayesian network meta-analyses were conducted using netmeta package and random-effects model.
Results Seven studies comprising 7,770 participants were included. The relative risk (RR) of progression and death (P&D) was highest in C and B>NN>P/V/NR/O in decreasing order. RR of AE≥3 was highest in P>NR>O/NN/B/V/C in decreasing order. PARPI significantly improved PFS in patients with homologous-recombinant deficiency (HRD) + or -, BRCA + or -, BRCA2+, and Stages 3 and 4. PARPI demonstrated an equivalent reduction in RRP&D in BRCA+ patients. In HRD+, O had the lowest RRP&D followed by NR then V in increasing order. However, in HRD-, V had the lowest RRP&D followed by NR then O.
Conclusions This network meta-analysis is the first to compare and rank firstline maintenance therapies in aOC. It indicates that PARPI have better outcomes than AA. It also demonstrates that individual PARPI vary in frequency of AE≥3 as well as clinical efficacy across mutation subtypes.