Health Canada has approved nivolumab (Opdivo) for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection.1
The approval’s basis comes from the randomized, double-blind phase 3 CheckMate -274 trial (NCT02632409), which evaluated nivolumab (240 mg) in 353 patients vs 356 patients receiving placebo.2 Patients who received nivolumab had a median disease-free survival of 20.8 months vs 10.8 months in the placebo arm.2
“For years, patients with muscle-invasive urothelial carcinoma have lived with the unfortunate reality that, despite being diagnosed early enough to have their cancer removed, more than fifty percent face disease recurrence, with few safe and effective treatment options available to improve outcomes in these patients,” said Wassim Kassouf, MD, professor, Department of Surgery (Urologic Oncology), McGill University. “The approval of Opdivo is particularly important because clinicians now have an immunotherapy option to offer certain patients after surgery, that may reduce the risk of disease recurrence. This approval has the potential to significantly impact the way we treat muscle-invasive urothelial carcinoma in Canada.”
Additional findings from the CheckMate-274 study indicated that 74.5% of patients in the nivolumab arm who had a PD-L1 expression of 1% or higher were alive and disease-free at 6-months vs 55.7% of those in the placebo (HR, 0.55; P < .001). A subgroup analysis identified a higher probability of DFS following treatment with nivolumab vs placebo regardless of nodule or PD-L1 status or use or non-use of previous neoadjuvant chemotherapy. At the database lock, 83.6% of patients were still receiving nivolumab or the placebo.
Moreover, investigators reported a median survival free from recurrence outside of the urothelial tract of 22.9 months for the nivolumab ITT population and 13.7 months for the placebo ITT population. At the 6-month follow-up, 77.0% in the nivolumab group and 62.7% in the placebo group were alive and disease free (HR, 0.72). Among patients who had a PD-L1 expression of 1% or more, 75.3% in the nivolumab group and 56.7% in the placebo group were alive and free from recurrence outside the urothelial tract at 6 months (HR, 0.55).
Treatment with nivolumab also yielded a longer median distant metastasis-free survival (MFS) of 40.5 months, and 29.5 months for the placebo group. Investigators also reported a 6-month distant MFS of 82.5% and 69.8% in both the nivolumab and placebo cohort, respectively (HR, 0.75). Those who had a PD-L1 expression of 1% or more had a 6-month distant MFS of 78.7% and 65.7% in both groups, respectively (HR, 0.61).
Adverse effects (AEs) occurred in 98.9% of patients who were treated with adjuvant nivolumab and 95.4% of those who received the placebo. AEs that were grade 3 or higher occurred in 42.7% of patients in the nivolumab arm and 36.8% in the placebo arm.
1. Health Canada Approves OPDIVO® (nivolumab) as Monotherapy for the Adjuvant treatment of Adults with Urothelial Carcinoma (UC) at High Risk of Recurrence after Undergoing Radical Resection of UC. Published online Juen 28, 2022. Accessed July 8, 2022. https://www.bms.com/ca/en/media/press-release-listing/2022-06-28-press-release.html
2. Bajorin DF, Witjes JA, Gschwend JE, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med. 2021;384(22):2102-2114. doi:10.1056/NEJMoa2034442