Extended CheckMate-274 Results Show Continued Benefit With Nivolumab in MIBC
Date: February 14, 2025
Author: Dr. Matthew I. Milowsky, MD, FASCO, University of North Carolina School of Medicine
Key Points:
- Extended 3-year follow-up from the CheckMate-274 trial has demonstrated ongoing benefits with adjuvant nivolumab over placebo in patients with muscle-invasive bladder cancer (MIBC).
- The trial previously confirmed a significant and clinically meaningful improvement in disease-free survival (DFS) for patients with high-risk muscle-invasive urothelial carcinoma, regardless of neoadjuvant chemotherapy (NAC) status.
- An interim analysis of overall survival (OS) showed that the median OS was not reached in the nivolumab group, in contrast to 39.9 months in the placebo group (HR 0.70, 95% CI [0.55, 0.90]).
- These findings were highlighted at the 2025 ASCO Genitourinary Cancers Symposium (Abstract 658), showing consistent benefits in DFS and OS regardless of prior NAC status.
Quotes:
- Dr. Matthew I. Milowsky: “The 3-year follow-up data from this practice-changing adjuvant immunotherapy trial in patients with high-risk [MIBC] continues to show a benefit for the use of nivolumab.”
- Dr. Elizabeth R. Plimack: “This study showed a really impressive result for an adjuvant study, with an [OS] benefit that continues to improve over time.”
Continued DFS Benefit:
The CheckMate-274 trial, a phase 3 study, had previously established a significant DFS benefit with adjuvant nivolumab:
- Study Population:
- Full intention-to-treat (ITT) cohort: 353 patients on nivolumab vs. 356 on placebo.
- MIBC cohort: 279 patients on nivolumab vs. 281 on placebo.
- DFS Results:
- Median DFS was 25.6 months with nivolumab compared to 8.5 months with placebo (HR 0.63, 95% CI [0.51, 0.78]).
- At 36 months, the DFS rate was 46.8% for nivolumab and 32.0% for placebo.
- NAC Status:
- With prior NAC: Median DFS was 19.6 months (nivolumab) vs. 8.3 months (placebo); HR 0.58 (95% CI [0.43, 0.79]).
- Without prior NAC: Median DFS was 25.9 months (nivolumab) vs. 13.7 months (placebo); HR 0.69 (95% CI [0.50, 0.94]).
Promising OS Trend:
- The interim OS analysis indicated that the median OS was not reached in the nivolumab group vs. 39.9 months in the placebo group (HR 0.70, 95% CI [0.55, 0.90]).
- At 36 months, OS rates were 64.2% for nivolumab and 53.7% for placebo.
- Benefit was consistent across NAC statuses.
PD-L1 Expression and OS:
- About 40% of patients in the nivolumab group and 41% in the placebo group had PD-L1 expression ≥1%.
- For PD-L1-positive patients, OS was not reached with nivolumab vs. 37.6 months with placebo (HR 0.48, 95% CI [0.29, 0.77]).
- 36-month OS rate was 71.8% for nivolumab vs. 52.0% for placebo in PD-L1-positive patients.
Safety Profile:
- No new safety signals were identified. Treatment-related AEs leading to discontinuation were observed in 15% of nivolumab patients vs. 2% in placebo.
- Common grade 3+ AEs included increased lipase (5%) and amylase (4%). Common AEs of any grade were pruritus (23%), fatigue (18%), and diarrhea (18%).
Future Directions:
- Dr. Plimack mentioned the MODERN study (NCT05987241) which is looking into circulating tumor DNA as a biomarker for adjuvant immunotherapy.
- She also pointed out that newer treatments like enfortumab vedotin and pembrolizumab might influence future OS outcomes.
Conclusion:
Dr. Milowsky concluded, “The fact that the study continues to demonstrate significant improvement in disease-free survival, and that this interim overall survival data looks very promising, is very exciting.”
Note: This post aims to consolidate and present the key findings and expert opinions from the CheckMate-274 trial on the use of nivolumab in MIBC, providing an overview for medical professionals and those interested in oncology research.
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