The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of nivolumab (Opdivo) for the adjuvant treatment of adults with muscle-invasive urothelial carcinoma with tumor cell PD-L1 expression ≥1% who are at a high risk of recurrence after undergoing radical resection.1
The CHMP based its recommendation on results from the randomized, double-blind phase 3 CheckMate -274 trial (NCT02632409), which evaluated nivolumab (n =353) vs placebo (n = 356).2,3 Patients who received nivolumab had a median disease-free survival of 20.8 months (95% CI, 16.5 to 27.6) vs 10.8 months (95% CI, 8.3 to 13.9) in the placebo arm (HR, 0.70; 95% CI, 0.57-0.86; P =.0008).
The European Commission will now review the opinion and make a final decision on approval. An approval would make nivolumab commercially available for this indication in the European Union, as well as Iceland, Norway, and Liechtenstein.
"Undergoing radical resection for high-risk muscle-invasive urothelial carcinoma can have a major impact on a patient’s quality of life. Unfortunately, due to limited adjuvant treatment options, approximately 50% of patients experience recurrence despite enduring this significant surgery," Dana Walker, MD, vice president, development program lead, genitourinary cancers, Bristol Myers Squibb, stated in a news release.
"Based on the results of the CheckMate -274 trial, Opdivo is the first and only immunotherapy to significantly extend disease-free survival for high-risk patients with muscle-invasive urothelial carcinoma. The CHMP’s positive recommendation brings us one step closer to providing patients in the European Union a chance to change the course of their disease at an early stage with an effective and tolerable adjuvant immunotherapy option," added Walker.
Additional findings from the 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.
The US FDA approved nivolumab for this indication in August 2021.
1. Bristol Myers Squibb Receives Positive CHMP Opinion Recommending Approval for Opdivo (nivolumab) as Adjuvant Treatment for Patients with Radically Resected, High-Risk Muscle-Invasive Urothelial Carcinoma with Tumor Cell PD-L1 Expression ≥1%. Published online February 25, 2022. Accessed February 25, 2022. https://yhoo.it/3pgQD1k.
2. U.S. Food and Drug Administration approves Opdivo (nivolumab) for the adjuvant treatment of patients with high-risk urothelial carcinoma. News release. Bristol Myers Squibb. August 20, 2021. Accessed August 20, 2021. https://bit.ly/3y8Yfo5
3. 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.