In the phase II NSGO-AVANOVA2/ENGOT-ov24 trial reported in The Lancet Oncology, Mansoor Raza Mirza, MD, and colleagues found that the combination of bevacizumab plus niraparib prolonged progression-free survival vs niraparib alone in women with platinum-sensitive recurrent ovarian cancer.

Mansoor Raza Mirza, MD

Study Details

The open-label trial included 97 women with high-grade serous or endometrioid platinum-sensitive recurrent ovarian cancer from 15 sites in Denmark, Sweden, Finland, Norway, and the United States. Patients were randomly assigned between May 2016 and March 2017 to receive bevacizumab 15 mg/kg once every 3 weeks plus niraparib 300 mg once daily (n = 48) or niraparib alone (n = 49) until disease progression or unacceptable toxicity. Randomization was stratified by homologous recombination deficiency (HRD) status and chemotherapy-free interval. Patients had received platinum-containing therapy for primary disease and had to have received at most one prior nonplatinum-containing regimen for recurrent disease. Previous treatment with bevacizumab or first-line maintenance poly (ADP ribose) polymerase inhibitors was permitted.

The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population after events in at least 62 patients.

Progression-Free Survival

Analysis was performed after 74 progression-free survival events. Median follow-up was 16.9 months. Median progression-free survival was 11.9 months (95% confidence interval [CI] = 8.5–16.7 months) in the bevacizumab/niraparib group vs 5.5 months (95% CI = 3.8–6.3 months) in the niraparib group (hazard ratio [HR] adjusted for stratification factors = 0.35, P < .0001). Median progression-free survival was 11.3 vs 4.2 months (HR = 0.32, 95% CI = 0.17–0.58) among 64 patients without germline BRCA mutations and 14.4 vs 9.0 months (HR = 0.49, 95% CI = 0.21–1.15) among patients with BRCA mutations.

Objective response rates were 60% vs 27% (P = .001). Overall survival data were immature at data cutoff. Death had occurred in eight patients in the bevacizumab/niraparib group and 13 patients in the niraparib group.

Adverse Events

Adverse events of grade ≥ 3 occurred in 65% of the combination group vs 45% of the niraparib group, with the most common in the combination group being hypertension (21% vs 0%),  anemia (15% vs 18%), thrombocytopenia (10% vs 12%), and neutropenia (8% vs 2%). The combination group had higher rates of any-grade hypertension (56% vs 22%) and proteinuria (21% vs 0%). No treatment-related deaths were observed.

The investigators concluded, “The efficacy observed with this chemotherapy-free combination of approved agents in women with platinum-sensitive recurrent ovarian cancer warrants further evaluation. A randomised phase III trial investigating niraparib plus bevacizumab vs chemotherapy plus bevacizumab in platinum-sensitive recurrent ovarian cancer is planned.”

Dr. Mirza, of Rigshospitalet Copenhagen University Hospital, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the Nordic Society of Gynaecological Oncology and Tesaro. For full disclosures of the study authors, visit thelancet.com.