In the phase II TITAN-RCC trial reported in The Lancet Oncology, Grimm et al found that a strategy of nivolumab monotherapy with or without nivolumab/ipilimumab as an immunotherapeutic boost was associated with activity in patients with metastatic clear cell renal cell carcinoma.
In the trial, 207 patients with intermediate- or poor-risk disease from sites in eight European countries were enrolled between October 2016 and November 2018, with 109 receiving first-line treatment and 98 receiving second-line treatment. Patients received nivolumab at 240 mg once every 2 weeks. Those with progressive disease at week 8 or no objective response at week 16 received two or four doses of nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg boosts once every 3 weeks; responders continued with nivolumab at 240 mg every 2 weeks and could receive two to four boost doses of nivolumab/ipilimumab for subsequent progressive disease. The primary endpoint was objective response rate; a rate of > 25%—based on results with nivolumab monotherapy in the pivotal CheckMate-025 trial—was required to reject the null hypothesis.
Median follow-up was 27.6 months (interquartile range = 10.5–34.8 months).
Objective responses were observed in 39 (36%, 90% confidence interval [CI] = 28%–44%, P = .0080 vs null hypothesis) of 109 patients in the first-line group and 31 (32%, 90% CI = 24%–40%, P = .083 vs null hypothesis) of 98 in the second-line group with nivolumab with or without nivolumab/ipilimumab boosting.
Objective response with nivolumab at week 8 or 16 was observed in 31 (28%) of 109 patients in the first-line group and 18 (18%) of 98 patients in the second-line group. A total of 24 (22%) of the first-line patients and 31 (32%) of the second-line patients received nivolumab/ipilimumab boosts after week 8 and 26 (24%) and 30 (31%), respectively, received boosts after week 16.
Among first-line responders, median duration of response was 30.7 months (95% CI = 12.2 months to not estimable). Among second-line responders, median duration of response was 18.8 months (95% CI = 11.2 months to not estimable).
The most common grade 3 or 4 treatment-related adverse events among all patients were increased lipase (7%), colitis (6%), and diarrhea (6%). Three deaths were considered to be treatment-related, due to ischemic stroke, respiratory failure, and pneumonia.
The investigators concluded, “In treatment-naive patients, nivolumab induction with or without nivolumab plus ipilimumab boosts significantly improved the objective response rate compared with that reported for nivolumab monotherapy in the CheckMate-025 trial. However, overall efficacy seemed inferior when compared with approved upfront nivolumab plus ipilimumab. For second-line treatment, nivolumab plus ipilimumab could be a rescue strategy on progression with approved nivolumab monotherapy.”
Marc-Oliver Grimm, MD, of the Department of Urology, Jena University Hospital, Friedrich-Schiller University, Jena, Germany, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Bristol Myers Squibb. For full disclosures of the study authors, visit thelancet.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.