Efficacy of niraparib in patients with advanced ovarian cancer: A meta-analysis of randomized controlled trials.

person Alice Marinho Federal University of the State of Rio de Janeiro, Rio De Janeiro, Brazil info_outline Alice Marinho, Eduardo Lambert Fossen, Maria Carolina Caldeira de Freitas, Gabriela Coelho Itaya, Larissa Maria Da Costa, Yasmin Dias, Davi Said Gonçalves Celso, Marcela Bonalumi Dos Santos, Mariana De Souza, Maysa Vilbert

Authors person Alice Marinho Federal University of the State of Rio de Janeiro, Rio De Janeiro, Brazil info_outline Alice Marinho, Eduardo Lambert Fossen, Maria Carolina Caldeira de Freitas, Gabriela Coelho Itaya, Larissa Maria Da Costa, Yasmin Dias, Davi Said Gonçalves Celso, Marcela Bonalumi Dos Santos, Mariana De Souza, Maysa Vilbert Organizations Federal University of the State of Rio de Janeiro, Rio De Janeiro, Brazil, Faculdade Santa Marcelina, Sao Paulo, Brazil, University of Brasilia, Brasilia, Brazil, University of South Santa Catarina, Tubarao, Brazil, Federal University of Acre, Rio Branco, Brazil, Washington University in St. Louis, St. Louis, MO, Federal University of Viçosa, Viçosa, Brazil, Oncoclinicas & Co - Medica Scientia Innovation Research (MEDSIR), São Paulo, Brazil, Federal University of Parana, Curitiba, Brazil, Massachusetts General Hospital Cancer Center, Boston, MA Abstract Disclosures Research Funding No funding sources reported Background: Niraparib is a poly-adenosine diphosphate-ribose polymerase (PARP) inhibitor that has shown clinical benefits as a maintenance therapy for patients with advanced ovarian cancer. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy of niraparib as maintenance therapy after platinum-based chemotherapy for patients with advanced ovarian cancer. PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched for RCTs published up to January 17, 2024. Hazard ratios (HR) and Odds ratio (OR) with 95% confidence intervals (CI) were pooled using a random-effects model. The endpoints of interest were time to first subsequent therapy (TFST) and progression-free survival (PFS). We performed subgroup analyses for BRCA-mutation, HRD-positive, HRD-negative, response to platinum therapy, and newly diagnosed disease. Results: Four RCTs were included, comprising a total of 1,935 patients of whom 1,291 received niraparib and 644 received placebo. Niraparib significantly improved PFS in the overall population (HR 0.45; 95% CI 0.31-0.66; p < 0.0001; I2= 82%), in patients with BRCA mutation (HR 0.32; 95% CI 0.25-0.43; p < 0.00001; I2= 21%), HRD positivity (HR 0.39; 95% CI 0.30-0.51; p < 0.00001; I2= 40%), HRD negativity (HR 0.45; 95% CI 0.36-0,57; p < 0.00001; I2= 0%), and newly diagnosed cancer (HR 0.59; 95% CI 0.39-0.73; p < 0.0001; I2= 68%). The TFST was longer in the niraparib group (HR 0.48; 95% CI 0.33-0.68; p < 0.0001; I2= 80%). There was no statistical difference between complete and partial response to platinum therapy (OR 1.00; 95% CI 0.87-0.1.16; p = 0.98; I2= 0%). Conclusions: Niraparib improves PFS and lowers the time to first subsequent therapy in patients with advanced ovarian cancer. Outcomes and results by studies. Study TFST (HR) Complete Response to Platinum Therapy (OR) Partial Response to Platinum Therapy (OR) Overall PFS (HR) PFS in BRCA-Mutation (HR) PFS in HRD-Positive (HR) PFS in HDR-Negative (HR) Newly Diagnosed (HR) PRIMA 2019 0.65 [0.52, 0.81] 0.97 [0.69, 1.35] 1.03 [0.74, 1.44] 0.62 [0.50, 0.77] 0.40 [0.27, 0.59] 0.43 [0.31, 0.60] 0.43 [0.31, 0.60] 0.62 [0.50, 0.77] PRIME 2023 0.45 [0.34, 0.60] 1.24 [0.72, 2.14] 0.80 [0.47, 1.38] 0.45 [0.34, 0.60] 0.40 [0.23, 0.70] 0.48 [0.34, 0.68] 0.48 [0.34, 0.68] 0.45 [0.34, 0.60] NOVA 2016 - 0.97 [0.68, 1.38] 1.03 [0.72, 1.48] - 0.27 [0.17, 0.43] 0.38 [0.24, 0.60] - - NORA 2021 0.35 [0.25, 0.49] 0.99 [0.59, 1.65] 1.06 [0.64, 1.76] 0.32 [0.23, 0.45] 0.22 [0.12, 0.40] 0.22 [0.12, 0.40] - - Total result (95% CI) 0.48 [0.33, 0.68] 1.01 [0.82, 1.23] 1.00 [0.82, 1.23] 0.45 [0.31, 0.66] 0.32 [0.25, 0.43] 0.39 [0.30, 0.51] 0.45 [0.36, 0.57] 0.54 [0.39, 0.73] p value < 0.0001 0.96 0.99 < 0.0001 < 0.00001 < 0.00001 < 0.00001 < 0.0001 TFST: time to first subsequent therapy; PFS: progression-free survival; OR: Odds ratio; HR: Hazard ratio; CI: confidence intervals.