Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)

Abstract

PURPOSE This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.

Remarkable Response to the Triplet Combination of Olaparib with Pembrolizumab and Bevacizumab in the Third-Line Treatment of an Ovarian Clear Cell Carcinoma Patient with an ARID1A Mutation: A Case Report

“…Subgroup analysis demonstrated a numerically longer overall survival with nivolumab compared with chemotherapy among patients with OCCC. 27 , 28 Taken together, these findings suggest that ICI monotherapy can induce responses in only a small subset of patients with OCCC. Several studies have proposed that PARP inhibitors can induce immunogenic tumor cell death, increase tumor neoantigens, upregulate PD-L1 expression, and, therefore, enhance the response to ICIs.…”

Evolution of Immunotherapy for Ovarian Cancer from a Bird’s-Eye Perspective: A Text-Mining Analysis of Publication Trends and Topics

“…The results revealed an active response in platinum-sensitive patients, but the response in platinum-resistant patients was still low, and no benefit was observed compared to the previous trial UMIN000005714. Nivolumab was also evaluated in comparison with gemcitabine or pegylated liposomal doxorubucin (PLD) for the treatment of platinum-resistant OC, but no treatment benefit in terms of improved overall survival was observed (JapicCTI-153004) ( 39 ).…”

Predicting Long-Term Prognoses and Grading Platinum Sensitivity Using a Novel Progression-Free Interval Criterion in Ovarian Clear Cell Carcinoma: A Multi-Institutional Cohort Study

“…Current trials evaluating the use of ICIs in ovarian cancer have not demonstrated improved survival [ 45 , 46 ]. Combination therapies with ICIs, chemotherapy regimens, PI3K/mTORC1/2 inhibitor [ 39 , 43 ], tyrosine kinase inhibitors [ 41 , 42 ], and/or PARP inhibitors [ 47 ] may be indicated for the treatment of advanced or relapsed OCCC.…”

“…Combination therapies with ICIs, chemotherapy regimens, PI3K/mTORC1/2 inhibitor [ 39 , 43 ], tyrosine kinase inhibitors [ 41 , 42 ], and/or PARP inhibitors [ 47 ] may be indicated for the treatment of advanced or relapsed OCCC. To date, there have been no positive correlations reported between treatment response and potential biomarkers related to the PI3K/mTOR or PD-1/PD-L1 pathways [ 44 , 45 , 46 ]. Hence, our stricter PFI criterion of grading platinum sensitivity for OCCC may be recommended for post-treatment surveillance.…”