The agency made the designation on the basis of recently reported data from the phase 3 CheckMate 274 trial that found a statistically significant improvement in disease-free survival in patients treated with the PD-1 inhibitor.
Bristol Myers Squibb announced the FDA's acceptance and granting of priority review for its supplemental biologics license application for nivolumab (Opdivo) as adjuvant therapy for patients with surgically resected, high-risk muscle-invasive urothelial carcinoma.1
This designation was granted based on data from the pivotal phase 3 CheckMate 274 trial (NCT02632409), a randomized, double-blind, multicenter study examining the efficacy of the PD-1 inhibitor as adjuvant therapy versus placebo in the indicated patient population.
“After patients undergo surgery for muscle-invasive urothelial carcinoma, they continue to face uncertainties given the high rate of disease recurrence and the lack of safe and effective treatment options,” Dana Walker, MD, MSCE, vice president and development program lead of genitourinary cancers at Bristol Myers Squibb, said in a press release. “Based on the ground-breaking disease-free survival results from CheckMate-274, we believe Opdivo has the potential to change the future of treatment for muscle-invasive urothelial carcinoma. We look forward to working with the FDA towards the goal of bringing the first adjuvant immunotherapy option to these patients in the US.”
Results of the trial were previously reported at the 2021 Genitourinary Cancers Symposium, with the experimental arm showing a statistically significant improvement in the primary end point of disease-free survival (DFS).2
Investigators found that the experimental therapy following surgery resulted in a 30% reduction in the risk of disease recurrence or death in the intent-to-treat (ITT) population (HR, 0.70; 98.31% CI, 0.54-0.89; P < .001). In patients with PD-L1–positive tumors, or those with expression of at least 1%, the reduction in risk of disease recurrence or death was 47% (HR, 0.53; 98.87% CI, 0.34-0.84; P < .001). Numerically, median DFS in the ITT population was better with nivolumab at 21.0 months versus 10.9 months with placebo. In the PD-L1 positive population, median DFS was not reached with nivolumab compared with 10.8 months in the placebo group.
A secondary end point of non–urothelial tract recurrence-free survival was improved with nivolumab for patients in the ITT population (HR, 0.72; 95% CI, 0.58-0.89) and PD-L1–positive subgroup (HR, 0.54; 95% CI, 0.38-0.77).
“Nivolumab is the first systemic immunotherapy to demonstrate a statistically significant and clinically meaningful improvement in outcomes when administered as adjuvant therapy to patients with muscle-invasive urothelial carcinoma,” lead author Dean Bajorin, MD, the Frederick R. Adler Senior Faculty Chair at Memorial Sloan Kettering Cancer Center in New York, New York, said during a presentation of the data at the symposium. “These results support nivolumab monotherapy as a new standard of care in the adjuvant setting for patients with high-risk MIUC after radical surgery regardless of PD-L1 status and prior neoadjuvant chemotherapy.”
Patients recruited to the trial (n = 709) were randomized 1:1 to receive adjuvant nivolumab at 240 mg every 2 weeks or placebo for up to 1 year. Eligible patients had radical surgery within 120 days and were disease-free as evidenced by imaging. Experience with neoadjuvant cisplatin was allowed, but was not required.
The median follow-up times for the nivolumab (n = 353) and placebo (n = 356) arms were 20.9 months and 19.5 months, respectively. In the nivolumab arm, 53.3% of patients discontinued treatment versus 56.3% in the placebo arm, and was most commonly due to disease recurrence. The safety profile of the experimental regimen was consistent with the known safety profile of the agent in patients with solid tumors.
The target action date for a decision of this application was set by the FDA as September 3, 2021.
1. U.S. Food and Drug Administration Accepts for Priority Review Bristol Myers Squibb’s Application for Opdivo (nivolumab) as Adjuvant Treatment for Patients with Muscle-Invasive Urothelial Carcinoma. News release. Bristol Myers Squibb. April 30, 2021. Accessed April 30, 2021. https://bit.ly/3xB7QoG
2. Bajorin DF, Witjes JA, Gschwend J, Schenker M. First results from the phase 3 CheckMate 274 trial of adjuvant nivolumab vs placebo in patients who underwent radical surgery for high-risk muscle-invasive urothelial carcinoma (MIUC). J Clin Oncol. 2021;39(suppl 6):391. doi:10.1200/JCO.2021.39.6_suppl.391