826P Comparative efficacy of first-line maintenance PARP inhibitors (PARPI) in advanced ovarian cancer (OC): A network meta-analysis

Abstract

Most newly diagnosed women with advanced OC relapse within 3 years despite surgical resection and adjuvant platinum-based chemotherapy. Many studies explored the clinical benefit of PARPI and antiangiogenic agents (AA) as maintenance agents with varied results. This analysis was conducted to update and expand our current knowledge of the relative efficacy of first-line maintenance PARPI as they relate to one another, and as they compare to first-line AA in advanced OC. A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of advanced ovarian cancer; first-line maintenance treatment with Olaparib (O), Niraparib (NR), Veliparib (V), Bevacizumab (B), Pazopanib (P), Nintedanib (NN), and control (C); and phase III randomized studies reporting progression, death, and adverse (AE) events. A frequentists and Bayesian network meta-analyses were conducted using netmeta package and random-effects model. Seven studies comprising a total of 7,770 participants were included. The relative risk (RR) of death and progression was highest in C and B than in NN, P, V, NR, and O in decreasing order. RR of AE≥3 was highest in P than NR, O, NN, B, V, and C in decreasing order. PARPI significantly improved PFS in homologous-recombinant deficiency (HRD+), HRD-, BRCA mutation (BRCA+), BRCA-, BRCA2+, Stage 3, and Stage 4 subgroups. PARPI demonstrated an equivalent reduction in RR of death and progression in BRCA+ patients. In HRD+, O had the lowest RR followed by NR, V, and C in increasing order. However, in HRD-, V had the lowest RR followed by NR and then O which seemed to be equivalent to C. This network meta-analysis is the first to compare and rank first-line maintenance treatment therapies in advanced OC. 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.