FDA Gives Nivolumab Priority Review Designation for Urothelial Carcinoma

Nivolumab (Opdivo) has received a priority review designation from the FDA as a treatment for patients with locally advanced unresectable or metastatic urothelial carcinoma.

Vicki Goodman, MD

Vicki Goodman, MD

Nivolumab (Opdivo) has received a priority review designation from the FDA as a treatment for patients with locally advanced unresectable or metastatic urothelial carcinoma following progression on a platinum-containing therapy, based on findings from the phase II CheckMate-275 study. The agency is scheduled to make a decision on the application for the PD-1 inhibitor by March 2, 2017, as part of the Prescription Drug User Fee Act (PDUFA).

In the study, which was presented at the 2016 ESMO Annual Meeting, the objective response rate (ORR) was 19.6% for nivolumab in patients with platinum-refractory metastatic urothelial carcinoma. 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.

“We are pleased that the FDA has accepted our application for Opdivo in previously treated patients with metastatic urothelial carcinoma, an advanced form of bladder cancer,” Vicki Goodman, MD, development lead, Melanoma and Genitourinary Cancers, Bristol-Myers Squibb, said in a statement. “We look forward to working with regulatory authorities to potentially bring Opdivo to this patient community, which has historically had limited treatment options.”

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. Nivolumab was administered at 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity.

The median age of patients was 66 years and 84.1% of patients had visceral metastases at baseline. Overall, 42.2% of patients had received 1 prior therapy and 29.3% had received ≥2 prior treatment regimens in the metastatic setting. PD-L1 expression ≥1% and ≥5% was reported for 45.9% and 30.7% of patients, respectively.

After a median follow-up of 7 months, 24.4% of patients remained on therapy. The median duration of response was not yet reached, with 76.9% 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% and a partial response rate of 17.4%. The stable disease rate was 22.6%.

In those with PD-L1 expression on &ge;1% of cells (n = 122), the ORR was 23.8% with nivolumab (95% CI, 16.5-32.3). In those with PD-L1 expression on &ge;5% (n = 81), the ORR was 28.4% (95% CI, 18.9-39.5). Additionally, responses were seen in patients with PD-L1-negative disease (n = 143), which was defined as PD-L1 expression on <1% of cells (ORR, 16.1%; 95% CI, 10.5-23.1).

&ldquo;Although higher PD-L1 expression was associated with numerically higher ORR and OS, even patients with low to no PD-L1 expression had an ORR which exceeded 10%,&rdquo; lead investigator Matthew D. Galsky, MD, professor of Medicine at the Mount Sinai School of Medicine, said when he presented the results at the ESMO Meeting. &ldquo;In patients with advanced urothelial carcinoma who have progressed despite prior platinum-containing chemotherapy, nivolumab demonstrated clinically meaningful efficacy, and has the potential to become a new standard of care.&rdquo;

Across the full study, treatment-related adverse events (AEs) were experienced by 64.4% of patients, with 17.8% of these events being grade 3/4 in severity. Overall, 4.8% of patients discontinued therapy due to treatment-related AEs, of which 3.0% 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%), pruritus (9.3%), diarrhea (8.9%), decreased appetite (8.1%), hypothyroidism (7.8%), nausea (7.0%), asthenia (5.9%), rash (5.9%), and pyrexia (5.6%). The most common grade 3/4 AEs were fatigue (1.9%), diarrhea (1.9%), asthenia (1.5%), and rash (1.1%).

&ldquo;The safety profile of nivolumab was associated with a low rate of treatment-related grade 3/4 toxicities, consistent with data in other tumor types, and quality-of-life was maintained,&rdquo; said Galsky.

In June 2016, the FDA granted nivolumab 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 II variation application for use of nivolumab for the same indication in September 2016.


Galsky MD, Retz M, Siefker-Radtke AO, et al. Efficacy and safety of nivolumab monotherapy in patients with metastatic urothelial cancer (mUC) who have received prior treatment: Results from the phase II CheckMate-275 study. Presented at: 2016 ESMO Congress; October 7-11, 2016; Copenhagen, Denmark. Abstract LBA31.

In patients with PD-L1 expression on &ge;1% 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.

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