CheckMate274 is a phase 3, randomized, double-blind, multicenter trial comparing nivolumab and placebo in a 1:1 randomized fashion among patients with high-risk muscle-invasive urothelial carcinoma (with primary tumor sites including bladder, ureter, or renal pelvis) after radical surgery.
Patients randomized to receive nivolumab were administered nivolumab 240mg every 2 weeks for up to 1 year of adjuvant therapy. All patients had to have radical surgery (cystectomy or nephroureterectomy) within 120 days of randomization. Patients were allowed but not required to have received neoadjuvant cisplatin. Patients who were ineligible for or declined cisplatin-based chemo were also included. Additionally, patients were required to have urothelial histology and be at high risk of recurrence based on pathologic staging and be disease-free based on imaging prior to randomization. Finally, only patients with ECOG performance status of 0 or 1 were included.
The primary outcomes of interest were disease-free survival (DFS) in all randomized patients (ITT population) and in patients with tumor PD-L1 expression ≥ 1%. Assessment of DFS was stratified by nodal status, receipt of prior neoadjuvant cisplatin, and PD-L1 status. A key secondary endpoint was non–urothelial tract recurrence-free survival (NUTRFS) among ITT patients and among those with PD-L ≥ 1%. Further, safety is an exploratory endpoint.
The authors accrued 709 patients, of whom 353 were randomized to nivolumab (of whom, 140 had PD-L1 ≥ 1%) and 356 were randomized to placebo (of whom 142 had PD-L1 ≥ 1%).
Over a median follow-up of approximately 20 months, median disease-free survival was significantly longer for patients receiving nivolumab (21 months) compared to placebo (11 months; hazard ratio 0.70, 95% confidence interval 0.54-0.89). A similar effect was observed in the PD-L1 ≥ 1% population (hazard ratio 0.53, 95% confidence interval 0.34-0.84).
The improvement in DFS was generally consistent across subgroups. Additionally, NUTRFS and distant metastasis-free survival were improved with the administration of nivolumab in both the ITT and PD-L1 ≥ 1% populations.
Further, grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 17.9% and 7.2% of patients in the nivolumab and placebo arms, respectively.
Finally, the authors assess health-related quality of life demonstrating no deterioration among those receiving nivolumab compared to placebo.
In conclusion, the authors demonstrate that adjuvant nivolumab is associated with both statistically significant and clinically meaningful improvement in DFS compared to placebo in patients with muscle invasive urothelial carcinoma following radical surgery, both in ITT patients and patients with PD-L1 ≥ 1%.
Presented by: Dean F. Bajorin, MD, Memorial Sloan Kettering Cancer Center (MSKCC)
Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center Contact: @WallisCJD on Twitter during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021
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