Adjuvant therapy with nivolumab was superior to placebo for improving disease-free survival in patients with muscle-invasive urothelial carcinoma.
Patients with muscle-invasive urothelial carcinoma (MIUC) benefitted from adjuvant nivolumab (Opdivo) in terms of improved disease-free survival (DFS) versus placebo, according to results of the phase 3 CheckMate 274 trial (NCT02632409).
Investigators found that nivolumab following surgery conferred a median DFS benefit in both the intent-to-treat (ITT) and PD-L1–positive populations. In the ITT population, DFS in those treated with nivolumab was 21.0 months compared with 10.9 months with placebo (HR, 0.70; 98.31% CI, 0.54-0.89; P < .001).
“This corresponds to a 30% reduction in the risk of disease recurrence or death with nivolumab,” 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 2021 ASCO Genitourinary Cancers Symposium. “The median DFS is nearly double with nivolumab compared to placebo.”
In the PD-L1 positive population, the median DFS in those treated with nivolumab was not reached compared with 10.8 months in the placebo group (HR, 0.53; 98.87% CI, 0.34-0.84; P < .001). “This corresponds to a 47% reduction in the risk of disease recurrence or death with nivolumab,” Bajorin said.
A subgroup analysis of the ITT population found there were no differences age, sex, region or performance status, he added.
The monoclonal antibody also improved median non–urothelial tract recurrence-free survival (NUTRFS), a secondary endpoint, and the exploratory endpoint of distant metastasis free survival (DMFS) in both the ITT and the PD-L1 positive patient populations.
In the ITT population, those treated with nivolumab experienced NUTRFS of 24.6 months versus 13.7 months in the placebo group (HR, 0.72; 95% CI, 0.58-0.89). In the PD-L1–positive population, NUTRFS in those treated with nivolumab was not reached versus 10.9 months in the placebo group (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,” he said. “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.”
The randomized, double- blind CheckMate-274 (NCT02632409) evaluated the efficacy and safety of adjuvant nivolumab versus placebo in patients with high-risk MIUC after radical surgery. Patients (N = 709) were randomized 1:1 to receive nivolumab 240 mg administered once every 2 weeks or placebo for up to 1 year of adjuvant treatment. Eligible patients had radical surgery within 120 days with or without neoadjuvant cisplatin or were ineligible/declined cisplatin-based chemotherapy, and were disease-free as evidenced by imaging.
The primary endpoint of the study was DFS in the ITT population and in patients with tumor PD-L1 expression ≥ 1%. The median follow-up was 20.9 months for nivolumab and 19.5 months for placebo.
In total, 353 patients were randomized to nivolumab and 356 patients to placebo. In the nivolumab arm, 53.3% of patients discontinued treatment, and in the placebo arm, 56.3% of patients discontinued. This was mostly commonly due to disease recurrence.
Among patients in the nivolumab arm, the tumor of origin was urinary bladder carcinoma in 79% of patients and upper tract disease in 21% of patients. In the placebo arm, the tumor of origin was urinary bladder in 78.9% of patients and upper tract disease in 21.1% of patients. About 40% patients in both arms were PD-L1 positive and about 43% had received prior cisplatin based neoadjuvant chemotherapy.
The safety of nivolumab was consistent with previously reported studies in patients with solid tumors. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 17.9% of patients in the nivolumab arm and 7.2% of patients in the placebo arm. Any-grade TRAEs leading to discontinuation occurred in 12.8% in the nivolumab arm and 2% of patients in the placebo arm. The most common TRAEs in the nivolumab arm were pruritis, fatigue, diarrhea, and rash.
Nivolumab is approved as a monotherapy for the treatment of platinum-resistant urothelial carcinoma.
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