Phase II study of maintenance niraparib rechallenge plus bevacizumab in patients with platinum-sensitive, recurrent ovarian cancer previously treated with a poly (ADP-ribose) polymerase inhibitor (KGOG-3056/NIRVANA-R)

초록

Objectives Maintenance poly (ADP-ribose) polymerase inhibitor (PARPi) rechallenge following response to platinum-based chemotherapy in platinum-sensitive relapsed ovarian cancer showed modest progression-free survival (PFS) benefit in the OReO/ENGOT-ov38 trial. We evaluated the efficacy and safety of maintenance niraparib rechallenge with bevacizumab. Methods NIRVANA-R was a multicenter, single-arm, phase II study (NCT04734665) evaluating niraparib rechallenge with bevacizumab in patients with platinum-sensitive recurrent ovarian cancer who had received prior PARP inhibitor. Patients who had responded to the last platinum regimen (either complete or partial response) were eligible to participate in this study. The primary endpoint was a six-month progression-free rate. The secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS). Genomic mechanisms of PARPi resistance from baseline circulating tumor DNA (ctDNA) were assessed by whole exome sequencing. Results Between 2019 and 2023, 44 patients were enrolled; more than 65 % of patients had received ≥3 lines of chemotherapy. At the primary data cutoff (June 1, 2024). The estimated six-month progression-free rate was 68 % (95 % CI 55–85 %). The main prognostic factors were treatment-free interval after penultimate platinum-based chemotherapy (TFIp) (TFIp ≥24 months vs TFIp <24 months; 82 % vs 56 %) and achieving a complete response (CR) (CR vs PR; 86 % vs 57 %) or normal CA-125 levels (CA-125 0–35 vs >35 U/mL; 72 % vs 25 %) to the most recent chemotherapy. The number of prior lines of chemotherapy (<3, ≥3), BRCA status, duration of prior PARPi exposure, type of previous PARPi (olaparib, niraparib, rucaparib), progression during/after PARPi and prior use of bevacizumab were not correlated with outcome. Median PFS was 11.5 months (95 % CI 7.9-NR). Treatment is still ongoing in 13 patients. Toxicity was expected with both drugs and no new safety signal was identified. Conclusions This is the first report of niraparib rechallenge with bevacizumab as a maintenance therapy in platinum-sensitive recurrent ovarian cancer patients previously treated with a PARPi. Promising activity was found with the doublet maintenance of niraparib plus bevacizumab and warrants further clinical research, in particular for patients who responded well to previous platinum-based chemotherapy such as having a long TFIp of 24 months, achieving a CR or normal CA-125 level to most recent chemotherapy.