Results from the phase 3 NINJA trial indicated that chemotherapy agents such as gemcitabine or pegylated liposomal doxorubicin yielded better survival outcomes vs nivolumab among patients with platinum-resistant ovarian cancer.
Treatment with chemotherapy agents such as gemcitabine (GEM) or pegylated liposomal doxorubicin (PLD) resulted in a better overall survival (OS) and progression-free survival (PFS) compared with nivolumab (Opdivo) in patients with platinum-resistant ovarian cancer, according to data from the phase 3 NINJA trial published in the Journal of Clinical Oncology.
At the data cutoff point of October 18, 2019, 131 patients in the nivolumab group and 125 in the chemotherapy group had died. The median OS was 10.1 months (95% CI, 8.3-14.1) and 12.1 months (95% CI, 9.3-15.3) in the nivolumab and chemotherapy groups, respectively (HR, 1.0; 95% CI, 0.8-1.3; P = .808). Subgroup analyses did not find any significant OS difference between the 2 groups, although OS was numerically longer for patients in the nivolumab group who had clear cell histology (HR, 0.78; 95% CI, 0.46-1.32) and those who received 1 chemotherapy regimen after platinum resistance diagnosis (HR, 0.74; 95% CI, 0.48-1.14).
“This phase 3 randomized controlled study investigated nivolumab monotherapy compared with chemotherapy in patients with platinum-resistant ovarian cancer,” the investigators wrote. “In this study, there was no statistical difference in OS between the groups, and ORR and PFS were worse with nivolumab versus chemotherapy.”
Female patients who were 20 years or older and had been diagnosed with epithelial ovarian cancer diagnosed plus platinum resistance were eligible for enrollment in the study. Eligibility criteria also required 1 or fewer treatments after platinum resistance diagnosis, an ECOG performance status of 1 or less, and available samples of tumor tissue for PD-L1 expression analysis. Additionally, patients were not able to receive prior treatment with nivolumab, gemcitabine or PLD, other anti–PD-1, anti–PD-L1, or anti–PD-L2 therapies.
The study’s primary end point was OS, with key secondary end points including PFS, best overall response, overall response rate (ORR), duration of response (DOR), time to response, quality of life, and safety.
Patients in the nivolumab group received 240 mg of intravenously nivolumab once every 2 weeks, and the chemotherapy group received either 1000 mg/m2 of intravenous gemcitabine for 30 minutes once on days 1, 8, and 15 or 50 mg/m2 ofPLD intravenously once every 4 weeks.
The intention-to-treat population included 316 patients who were randomly assigned to either the nivolumab group (n = 157) or chemotherapy group (n = 159). Additionally, 233 patients—119 in the nivolumab arm and 114 in the chemotherapy arm—and 311 patients—156 in the nivolumab arm and 155 in the chemotherapy arm—were featured in the response-evaluable set and safety analysis set, respectively.
The median PFS was 2.0 months (95% CI, 1.9-2.2) for patients in the nivolumab group vs 3.8 months (95% CI, 3.6-4.2) for patients in the chemotherapy group (HR, 1.5; 95% CI, 1.2-1.9; P = .002). A statistically significant difference in ORR was not observed between the nivolumab and chemotherapy groups (7.6% vs 13.2%, respectively; odds ratio [OR], 0.6; 95% CI, 0.2-1.3; P = .191).
A complete (CR) or partial responses (PR; defined as a 30% or greater reduction in tumor size) were reported in 9 patients in the nivolumab cohort and 15 patients in the chemotherapy cohort. Additionally, the median DOR was 18.7 months (95% CI, 2.5–not evaluable) for the nivolumab group and 7.4 months (95% CI, 3.0-10.3) for the chemotherapy group.
Incidence rate of any grade treatment-related adverse effects (TRAEs) was significantly lower for the nivolumab group (61.5%) compared with the chemotherapy group (98.1%). Common any grade TRAEs for the nivolumab group included rash (10.3%), fatigue (9.0%), and nausea (6.4%). In the chemotherapy group, common any grade TRAEs included neutrophil count decreased (64.5%), platelet count decreased (33.5%), and nausea (32.9%).
Grade 3 or 4 TRAEs were observed in 10.9% and 65.2% of patients in the nivolumab and chemotherapy groups, respectively. The most common grade 3 or 4 TRAE was anemia (2.6%) in the nivolumab group and decreasing neutrophil count (40.0%) in the chemotherapy group.
Hamanishi J, Takeshima N, Katsumata N, et al. Nivolumab versus gemcitabine or pegylated liposomal doxorubicin for patients with platinum-resistant ovarian cancer: open-label, randomized trial in Japan (NINJA). J Clin Oncol. 2021. doi:10.1200/JCO.21.00334