FDA OKs Adjuvant Nivolumab to Treat High-Risk Urothelial Carcinoma

The FDA approved adjuvant nivolumab (Opdivo) to treat patients with urothelial carcinoma who are at high risk of recurrence after undergoing radical resection, irrespective of prior neoadjuvant chemotherapy, nodal involvement or PD-L1 status, according to Bristol Myers Squibb.

The regulatory decision is based on data from the phase 3 CheckMate-274 trial (NCT02632409), in which the immunotherapy resulted in a median disease-free survival (DFS) that was nearly double that reported in those who received placebo, at 20.8 months (95% CI, 16.5-27.6) and 10.8 months (95% CI, 8.3-13.9), respectively. Nivolumab resulted in a 30% reduction in the risk of disease recurrence or death vs placebo (HR, 0.70; 95% CI, 0.57-0.86; P = .0008).

In the patients whose tumors had a PD-L1 expression of 1% or higher, the median DFS had not yet been reached (95% CI, 21.2–not evaluable) with nivolumab vs 8.4 months (95% CI, 5.6-21.2) with placebo. In this subset, the immunotherapy resulted in a 45% reduction in the risk of disease recurrence or death (HR, 0.55; 95% CI, 0.39-0.77; P = .0005).

“This approval is a major milestone for patients who have undergone major surgery to remove the bladder or parts of the urinary tract and are in need of additional treatment approaches that can help reduce the risk of their urothelial carcinoma returning,” Matthew D. Galsky, MD, primary trial investigator, professor of medicine, director of Genitourinary Medical Oncology, co-director of the Center of Excellence for Bladder Cancer, and associate director for Translational Research at The Tisch Cancer Institute and the Icahn School of Medicine at Mount Sinai, stated in a press release. “Nivolumab provides a new FDA-approved treatment shown to reduce the risk of disease recurrence or death based on the safety and efficacy findings from CheckMate-274, and has the potential to become a new standard-of-care option in this setting.”

The multicenter, double-blind, placebo-controlled CheckMate-274 trial enrolled patients with ypT2-ypT4a or yPN-positive muscle-invasive urothelial carcinoma (MIUC) who had received neoadjuvant cisplatin chemotherapy. Patients with pT3-pT4a or pN-positive MIUC who did not receive prior neoadjuvant cisplatin chemotherapy and were not candidates for or refused adjuvant cisplatin chemotherapy, were also permitted.

Additionally, patients were required to have undergone radical surgery within the past 120 days and to have disease-free status within 4 weeks of dosing on the trial.

Study participants were randomized 1:1 to receive intravenous (IV) nivolumab at a dose of 240 mg every 2 weeks (n = 351) or IV placebo every 2 weeks (n = 348). They received adjuvant treatment for up to 1 year.

Patients were stratified based on PD-L1 expression (<1% vs ≥1%), prior neoadjuvant cisplatin-based chemotherapy, and nodal status.

The primary end points of the trial were DFS in the intent-to-treat population and DFS in all randomized patients with a PD-L1 expression of 1% or higher. Key secondary end points comprised non–urothelial tract recurrence-free survival, disease-specific survival, and overall survival. Exploratory end points included distant metastasis-free survival, safety, and health-related quality of life (HRQoL).

Reference:

Bristol Myers Squibb. U.S. Food and Drug Administration Approves Opdivo® (nivolumab) for the Adjuvant Treatment of Patients with High-Risk Urothelial Carcinoma. Published August 20, 2021. https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-Opdivo-nivolumab-for-the-Adjuvant-Treatment-of-Patients-with-High-Risk-Urothelial-Carcinoma/default.aspx. Accessed August 20, 2021.