ASCO GU 2023: Extended Follow-up Results from the CheckMate 274 Trial

(UroToday.com) On the second day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2023 focussing on urothelial cancer, the Oral Abstract Session B included a presentation from Dr. Matt Galsky highlighting updated data from the CheckMate 274 trial with extended follow-up results examining adjuvant nivolumab for patients with resected muscle-invasive urothelial carcinoma.

As previously reported and published, the two primary endpoints of the CheckMate 274 trial were met as adjuvant nivolumab improved disease-free survival (DFS) versus placebo in both the intent-to-treat (ITT) population and in patients with tumor programmed death ligand 1 (PD-L1) expression ≥ 1%. This led to nivolumab becoming standard of care in this disease space. In a presentation at today’s ASCO-GU meeting, Dr. Galsky presented updated results from this trial.

As has previously been described, the CheckMate 274 trial is a phase 3, double-blind trial of adjuvant nivolumab versus placebo in patients with high-risk muscle-invasive urothelial carcinoma (MIUC) (bladder, ureter, or renal pelvis) after radical resection (NCT02632409). Patients were randomly assigned 1:1 to nivolumab 240 mg every 2 weeks or placebo for up to 1 year of treatment. To be eligible, patients had pathologic evidence of UC at high risk of recurrence and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1. While the two primary endpoints were DFS in ITT patients and in patients with PD-L1 ≥ 1%, DFS was also analyzed in prespecified subgroups.

Additionally, overall survival and non–urothelial tract recurrence-free survival (NUTRFS) in ITT patients and in patients with PD-L1 ≥ 1% were secondary endpoints. Finally, distant metastasis-free survival (DMFS) and safety were exploratory endpoints. Importantly, overall survival, a secondary endpoint, is to be tested using an event-driven hierarchical procedure.

The authors randomized 353 patients to nivolumab (PD-L1 ≥ 1%, n = 140) and 356 to placebo (PD-L1 ≥ 1%, n = 142). Over a median follow-up of 36.1 months (and a minimum follow-up of 31.6 months), the median DFS was 22.0 months with nivolumab versus 10.9 months with placebo in ITT patients and 52.6 months with nivolumab versus 8.4 months with placebo in patients with PD-L1 ≥ 1%.

Importantly, the DFS benefit was seen in most subgroups analyzed including age, sex, ECOG PS, nodal status, prior cisplatin-based chemotherapy, and PD-L1 status.

A similarly consistent benefit was seen across many tumor characteristics.

Considering secondary and exploratory endpoint, NUTRFS (ITT: HR 0.72, 95% CI 0.59-0.84; PD-L1≥2%: HR 0.53, 95% CI 0.38-0.74) and DMFS (ITT: HR 0.74, 95% CI 0.60-0.92; PD-L1≥2%: HR 0.58, 95% CI 0.40-0.84) benefits with nivolumab versus placebo were also observed in both populations, though overall survival data remained immature and will be assessed as a future data cut off. Summarizing the evolution of data across endpoints over time, Dr. Galsky noted the particularly consistent findings for each endpoint.

Grade 3–4 treatment-related adverse events occurred in 18.2% of patients randomized to nivolumab and 7.2% of patients randomized to placebo, consistent with the primary analysis.

Thus, Dr. Galsky concluded that this extended follow-up of CheckMate 274 demonstrates ongoing DFS, NUTRFS, and DMFS benefits of adjuvant nivolumab compared to placebo. Compared to the initial report of these data, the magnitude of the effect has increased somewhat for DFS and NUTRFS in PD-L1 ≥ 1% patients and for DMFS in both ITT and PD-L1 ≥ 1% patients without any additional safety signals.