KEY TAKEAWAYS
- The CheckMate 274 phase 3 trial aimed to evaluate the long-term impact of adjuvant nivolumab on OS in patients with bladder cancer.
- The primary endpoint was DFS, and non-urinary tract-free survival was the secondary endpoint.
- The extended follow-up confirmed adjuvant nivolumab’s survival benefit in high-risk urothelial carcinoma after radical resection.
Despite radical cystectomy, with or without neoadjuvant cisplatin-based chemotherapy, many patients with muscle-invasive urothelial carcinoma suffer a recurrence within 3 years. Nivolumab emerged as the standard adjuvant treatment for high-risk cases after radical surgery, following positive initial results from CheckMate 274.
This phase 3 trial evaluated adjuvant nivolumab’s efficacy in high-risk muscle-invasive urothelial carcinoma post-surgery. The trial met its primary endpoints, showing improved disease-free survival (DFS) with adjuvant nivolumab versus placebo in the intention-to-treat population and patients with PD-L1 expression >= 1%.
Dr. Galsky and the team aimed to provide the extended follow-up findings from CheckMate 274, marking the inaugural report on overall survival (OS) outcomes.
The study compared 1 year of adjuvant nivolumab with a placebo for high-risk muscle-invasive urothelial carcinoma. They enrolled patients with ypT2-ypT4a or ypN+ who had prior neoadjuvant cisplatin chemotherapy or pT3-pT4a or pN+ without prior neoadjuvant cisplatin chemotherapy and who were not eligible or declined adjuvant cisplatin chemotherapy.
The primary endpoint, disease-free survival (DFS), demonstrated continued improvement with nivolumab compared to placebo in both the intention-to-treat population (HR 0.71, 95% CI 0.58-0.86) and the PD-L1 > 1% populations (HR 0.52, 95% CI 0.37-0.72).
The analysis revealed that the interim OS outcomes showed a preference for nivolumab over placebo in the intention-to-treat analysis (HR 0.76, 95% CI 0.61-0.96) and the tumor PD-L1 > 1% populations (HR 0.56, 95% CI 0.36-0.86). OS across subgroups in the intention-to-treat population generally favored adjuvant nivolumab, notably among N+ and variant histology patients.
Non-urinary tract recurrence-free survival, a key secondary endpoint, and distant metastasis-free survival, a key exploratory endpoint, also leaned towards adjuvant nivolumab in both the intention-to-treat and PD-L1 > 1% patient populations.
The safety outcomes revealed that nivolumab-treated patients exhibited treatment-related adverse events (TRAEs) of any grade in 79% of cases, contrasting with 56% in the placebo group. Additionally, nivolumab administration was associated with a higher incidence of Grade 3+ adverse events (18% vs. 7%). Common AEs included pruritus, fatigue, diarrhea, and rash.
The extended follow-up from CheckMate 274 reaffirms adjuvant nivolumab’s superiority over placebo in disease-free, recurrence-free, and distant metastasis-free survival. OS benefits persist, further establishing nivolumab as a standard treatment for high-risk muscle-invasive urothelial carcinoma post-radical resection.
The trial was sponsored by Bristol-Myers Squibb.
Source: https://scientific-programme.uroweb.org/EAU24/programme
Clinical Trial: https://clinicaltrials.gov/study/NCT02632409
Galsky MD, Witjes JA, Gschwend JE, et al. (2024) “Extended Follow-up from CheckMate 274 Including the First Report of Overall Survival Outcomes.” Presented at EAU 2024.
