In the phase I/II CheckMate 032 trial reported in The Lancet Oncology, Padmanee Sharma, MD, of The University of Texas MD Anderson Cancer Center, and colleagues found that nivolumab (Opdivo) was active in locally advanced or metastatic urothelial carcinoma progressing after platinum-based therapy.
In the study, 78 patients with urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra were enrolled at 16 sites in Finland, Germany, Spain, UK, and United States between June 2014 and April 2015. Patients received nivolumab at 3 mg/kg every 2 weeks until disease progression or treatment discontinuation due to unacceptable toxicity or other protocol-defined reasons. The primary endpoint was objective response on investigator assessment.
Minimum follow-up at data cutoff was 9 months (median = 15.2 months). Objective response was achieved in 19 patients (24.4%, 95% confidence interval [CI] = 15.3%–35.4%) of 78 patients. Median time to response was 1.5 months, and median duration of response was 9.4 months; response was ongoing in 12 of 19 responders at the time of analysis.
Median overall survival was 9.7 months, and 1-year overall survival was 46%. Median progression-free survival was 2.8 months, and 1-year progression-free survival was 21%.
Retrospective analysis of response by PD-L1 (programmed cell death ligand 1) status showed response in 6 of 25 patients (24%) with PD-L1 expression ≥ 1% and 11 of 42 patients (26%) with expression < 1%. Median overall survival was 16.2 months and 9.9 months, and median progression-free survival was 5.5 months and 2.8 months.
Grade 3 or 4 treatment-related adverse events occurred in 22% of patients, with the most common being elevated lipase (5%); elevated amylase (4%); and fatigue, maculopapular rash, dyspnea, decreased lymphocyte count, and decreased neutrophil count (3% each). Serious adverse events were reported in 46% and were considered related to treatment in 10%. Two patients (3%) discontinued treatment due to treatment-related adverse events (grade 4 pneumonitis and grade 4 thrombocytopenia) and subsequently died.
The authors concluded: “Nivolumab monotherapy was associated with a substantial and durable clinical response and a manageable safety profile in previously treated patients with locally advanced or metastatic urothelial carcinoma. These data support further investigation of nivolumab monotherapy in advanced urothelial carcinoma.”
Bristol-Myers Squibb funded the study.