Study Evaluates Response-Based Immunotherapy Strategy in Patients With Advanced Urothelial Carcinoma

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In a phase II study (TITAN-TCC) reported in the Journal of Clinical Oncology, Grimm et al found that a nivolumab/ipilimumab boost in patients with advanced urothelial cancer who did not respond to nivolumab monotherapy alone increased objective response rates, with the benefit being greatest in those patients previously untreated (first-line), compared with patients who experienced disease progression during or following platinum-based therapy (second-line or third-line).

Study Details

The study enrolled 86 patients from sites in Austria and Germany between July 2017 and April 2019; a total of 68 had metastatic disease. All patients received nivolumab monotherapy at 240 mg once every 2 weeks for four doses, with responders continuing with nivolumab maintenance. Patients with stable/progressive disease after 8 weeks received nivolumab at 3 mg/kg plus ipilimumab at 1 mg/kg once every 3 weeks for two doses; those not responding to the initial boost received nivolumab at 1 mg/kg plus ipilimumab at 3 mg/kg once every 3 weeks for two doses. Patients responding to boosts continued with nivolumab maintenance.  

Among the 86 patients, 42 were receiving first-line treatment; 39, second-line; and 5, third-line.

Key Findings

Objective response with nivolumab monotherapy assessed at week 8 occurred in 12 (29%) of 42 first-line patients, including complete response in 1 (2%), and in 10 (23%) of 44 second- or third-line patients, with complete response in 1 (2%).

A total of 41 patients received nivolumab/ipilimumab boosts starting at week 8 and 11 received later boosts for disease progression. Boosting achieved objective response in an additional seven first-line patients, increasing the objective response rate to 45% (19 of 42), with complete response in three patients (7%). Boosting achieved objective response in an additional two second- or third-line patients, increasing the objective response rate to 27% (12 of 44), with no additional complete responses.

The investigators concluded, “The tailored approach of TITAN-TCC shows meaningful clinical activity supporting dual checkpoint inhibition in first-line treatment of metastatic urothelial carcinoma. However, starting therapy with nivolumab exclusively appears inadequate given the aggressive nature of metastatic urothelial carcinoma. In second/third-line treatment, nivolumab/ipilimumab boosts with escalating ipilimumab dose did not improve efficacy outcomes vs nivolumab monotherapy. An independent second-line cohort of TITAN-TCC receiving nivolumab [at] 1 mg/kg plus ipilimumab [at] 3 mg/kg once every 3 weeks for four doses is ongoing.”

Marc-Oliver Grimm, MD, of the Department of Urology, Jena University Hospital, Jena, Germany, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by Bristol Myers Squibb. For full disclosures of the study authors, visit

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