Opdivo was granted an accelerated approval for a subset of patients with urothelial carcinoma.
The U.S. Food and Drug Administration (FDA) granted Opdivo (nivolumab) an accelerated approval for patients who have locally advanced unresectable or metastatic urothelial carcinoma following progression on a platinum-containing therapy. The approval is based on findings from a phase 2 CheckMate-275 study.
In the study, which was presented at the 2016 ESMO Annual Meeting, the objective response rate (ORR) was 19.6 percent for Opdivo in patients with platinum-refractory metastatic urothelial carcinoma. The complete response rate was 3 percent. Across the 270-patient study, the median progression-free survival (PFS) was 2.0 months and the median overall survival (OS) was 8.74 months.
The open-label study enrolled 270 patients with metastatic or unresectable urothelial carcinoma. Patients had received a platinum-based agent in the metastatic setting or were within one year of neoadjuvant/adjuvant platinum therapy. Opdivo was administered at 3 mg/kg intravenously every two weeks until progression or unacceptable toxicity.
The median age of patients was 66 years and 84.1 percent of patients had visceral metastases at baseline. Overall, 42.2 percent of patients had received one prior therapy and 29.3 percent had received at least two prior treatment regimens in the metastatic setting. PD-L1 expression greater than 1 percent and greater than 5 percent was reported for 45.9 percent and 30.7 percent of patients, respectively.
After a median follow-up of seven months, 24.4 percent of patients remained on therapy. The median duration of response was not yet reached, with 76.9 percent of responses ongoing at the time of the analysis. The median time to response was 1.9 months. Responses consisted of a complete response rate of 2.3 percent and a partial response rate of 17.4 percent. The stable disease rate was 22.6 percent.
In those with PD-L1 expression on at least 1 percent of cells (122 patients), the ORR was 23.8 percent with Opdivo. In those with PD-L1 expression on at least 5 percent (81 patients), the ORR was 28.4 percent. Additionally, responses were seen in patients with PD-L1-negative disease (143 patients), which was defined as PD-L1 expression on less than 1 percent of cells.
In patients with PD-L1 expression on at least 1 percent of cells, the median PFS was 3.55 months and the median OS was 11.3 months. In those with PD-L1-negative tumors, the PFS was 1.87 months and the median OS was 5.95 months.
Across the full study, treatment-related adverse events (AEs) were experienced by 64.4 percent of patients, with 17.8 percent of these events being grade 3/4 in severity. Overall, 4.8 percent of patients discontinued therapy due to treatment-related AEs, of which 3.0 percent were grade 3/4 in severity. Quality-of-life, as assessed using the Global Health Status Scale, improved from baseline and remained stable over the course of the trial.
The most frequently reported all-grade AEs were fatigue (16.7 percent), pruritus (9.3 percent), diarrhea (8.9 percent), decreased appetite (8.1 percent), hypothyroidism (7.8 percent), nausea (7.0 percent), asthenia (5.9 percent), rash (5.9 percent) and pyrexia (5.6 percent). The most common grade 3/4 AEs were fatigue (1.9 percent), diarrhea (1.9 percent), asthenia (1.5 percent) and rash (1.1 percent).
In June 2016, the FDA granted Opdivo a breakthrough therapy designation for the treatment of patients with unresectable locally advanced or metastatic urothelial carcinoma after the failure of a platinum-containing regimen. The EMA validated a type 2 variation application for use of Opdivo for the same indication in September 2016.