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.
Study Details
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.
Key Findings
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.
