FDA Approves Nivolumab for High-Risk Urothelial Carcinoma

Urothelial carcinoma.

The FDA has granted regular approval to nivolumab (Opdivo®, Bristol Myers Squibb) as adjuvant therapy for patients with urothelial carcinoma who are at high risk of recurrence after undergoing radical resection. This is the first time the FDA has approved an adjuvant treatment for patients with high-risk urothelial carcinoma. Nivolumab had previously been granted accelerated approval for advanced and metastatic urothelial cancer.

“In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab or placebo,” wrote Dean F. Bajorin, MD, the Frederick R. Adler Senior Faculty Chair and a medical oncologist specializing in genitourinary tumors at Memorial Sloan Kettering Cancer Center, and colleagues, in their abstract of the results of the CHECKMATE-274 study (NCT02632409), on which the regular approval was based.

The clinical trial enrolled 709 patients with urothelial carcinoma who had undergone radical resection of the bladder or upper urinary tract within 120 days and who were at high risk of recurrence. Patients received either 240 mg nivolumab or placebo by intravenous infusion every two weeks for up to one year, until recurrence or unacceptable toxicity. The primary end point was disease-free survival; the secondary end point was survival free from recurrence outside the urothelial tract.

In the intent-to-treat population, the median disease-free survival was 20.8 months in the nivolumab treatment arm, which was significantly higher than 10.8 months in the placebo arm. For the patients with tumors expressing programmed death ligand-1 (PD-L1), median disease-free survival was not reached for patients receiving nivolumab, compared with 8.4 months for patients receiving placebo. The unstratified hazard ratio for disease-free survival was 0.83 in patients with PD-L1–negative tumors. In the overall randomized population, overall survival data is immature; among patients with upper tract urothelial cancer, 20 deaths have occurred in the nivolumab arm and 17 deaths in the placebo arm.

The most common adverse events occurring in at least 20% of patients in the CHECKMATE-274 study were rash, fatigue, diarrhea, pruritus, musculoskeletal pain, and urinary tract infection.

“In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression of 1% or more,” concluded Dr. Bajorin and colleagues in their June 2021 publication in The New England Journal of Medicine.

The recommended dose of nivolumab for adjuvant treatment of urothelial carcinoma is 240 mg every 2 weeks or 480 mg every 4 weeks.

For More Information

Bajorin DF, Witjes JA, Gschwend JE, et al (2021). Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med, 384(22):2102-2114. DOI:10.1056/NEJMoa2034442

Clinicaltrials.gov (2020). An investigational immuno-therapy study of nivolumab, compared to placebo, in patients with bladder or urinary tract cancer, following surgery to remove the cancer (CheckMate 274). NLM identifier: NCT02632409.

Opdivo® (nivolumab) prescribing information (2021). Bristol Myers Squibb. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125554s097lbl.pdf

US Food & Drug Administration (2021). FDA approves nivolumab for adjuvant treatment of urothelial carcinoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-adjuvant-treatment-urothelial-carcinoma

Image credit: CoRus13. Licensed under CC0 1.0

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