NINJA: Nivolumab does not improve OS vs gemcitabine or PLD in platinum-resistant ovarian cancer

Nivolumab does not improve overall survival (OS) in patients with platinum-resistant ovarian cancer when compared with standard second- and subsequent-line chemotherapy, according to the results of the phase III NINJA trial presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

The open-label, randomized, multicentre trial compared nivolumab (240 mg intravenously [IV] Q2W) against gemcitabine (1000 mg/m² IV for 30 minutes on days 1, 8, and 15, then Q4W) or pegylated liposomal doxorubicin (PLD; 50 mg/m² IV Q4W) for the treatment of advanced or recurrent platinum-resistant ovarian cancer in Japanese patients aged ≥20 years who have not been previously treated with gemcitabine or PLD. Treatment was continued until disease progression or toxicity leading to discontinuation. [Omatsu K, et al, ESMO 2020, abstract 807O]

The primary endpoint of median OS was 10.12 months in the nivolumab arm (n=157) vs 12.09 months in the gemcitabine or PLD arm (n=159), with no statistically significant difference between the groups (hazard ratio [HR], 1.03; 95 percent confidence interval [CI], 0.80 to 1.32; p=0.808).

“Of all subgroups analyzed, the OS with nivolumab was numerically longer than with gemcitabine or PDL in patients with clear-cell carcinoma [HR, 0.78; 95 percent CI, 0.46 to 1.32],” noted presenter Dr Kohei Omatsu of the Gynecologic Oncology Department at the Cancer Institute Hospital of Japanese Foundation for Cancer Research in Tokyo, Japan.

Median progression-free survival was 2.04 months in the nivolumab group vs 3.84 months for patients treated with gemcitabine or PLD (HR, 1.46; 95 percent CI, 1.15 to 1.85; p=0.002).

There was no statistically significant difference in response rates between the treatment groups, with responses observed in 8 percent of patients in the nivolumab group (n=9) vs 13 percent of gemcitabine- or PLD-treated patients (n=15) (odds ratio, 0.6; 95 percent CI, 1.02 to 1.3; p=0.191).

Notably, the median duration of overall response among responders was longer in the nivolumab group (18.7 months) vs gemcitabine or PLD group (7.4 months), echoing the results of the earlier phase II trial, which saw durable complete responses in two patients on nivolumab. [J Clin Oncol 2015;33:4015-2022]

Rates of grade 3/4 treatment-emergent adverse events (TRAEs) and all-grade TRAEs were lower in the nivolumab arm (11 percent and 62 percent, respectively) vs the gemcitabine or PLD arm (65 percent and 98 percent, respectively). The most common grade 3/4 TRAEs in the nivolumab arm were anaemia (3 percent vs 14 percent), neutropenia (1 percent vs 40 percent), increased alanine aminotransferase level (1 percent vs 1 percent), and anorexia (1 percent vs 2 percent). The most common all-grade TRAEs associated with nivolumab were rash (10 percent vs 7 percent), fatigue (9 percent vs 8 percent), nausea (6 percent vs 33 percent), diarrhoea (6 percent vs 6 percent), and pruritus (6 percent vs 4 percent).

“There were higher risks of toxicity with chemotherapy, but the efficacy results do not support the general use of checkpoint inhibition for recurrent platinum-resistant ovarian cancer,” commented discussant Professor Ursula Matulonis of the Division of Gynecologic Oncology at the Dana-Farber Cancer Institute in Boston, Massachusetts, US. “Some new strategies are really necessary.”