Skip to content
Bending the Curve Trial by Trial
?

CheckMate 274

Needs review

Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma

Phase 3N = 709NCT02632409

Population
Patients with high-risk muscle-invasive urothelial carcinoma (originating in the bladder, ureter or renal pelvis; upper-tract enrolment capped at about 20%) who had undergone radical surgery
Design
Phase 3, multicentre, double-blind randomised controlled trial (1:1): nivolumab 240 mg intravenously or placebo every 2 weeks for up to 1 year after radical surgery for muscle-invasive urothelial carcinoma. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. Primary end points: disease-free survival among all patients (intention-to-treat population) and among patients with tumour PD-L1 expression of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point.
Primary endpoint
DFS
Arms
  • Nivolumab (experimental, n = 353): Nivolumab 240 mg intravenously every 2 weeks for up to 1 year
  • Placebo (control, n = 356): Placebo every 2 weeks for up to 1 year
People
Bajorin DF, senior author Galsky MD
DFSHR 0.7Δ median DFS+10 monthsΔ 6-month DFS+14.6 pointsDFSHR 0.55Δ 6-month DFS+18.8 pointsSurvival free from recurrence outside the urothelial tractHR 0.72 (95% CI 0.59–0.89)
Show the numbers
Results reported for CheckMate 274
EndpointAnalysisNivolumabPlaceboEffect
DFSprimaryBajorin 2021median 20.8 months (16.5–27.6); 74.9% at 6 momedian 10.8 months (8.3–13.9); 60.3% at 6 moHR 0.7P<0.001Hazard ratio for disease recurrence or death; the abstract gives a 98.22% confidence interval of 0.55 to 0.90 (not a 95% interval). The 6-month values are the percentages alive and disease-free.
DFSPatients with tumour PD-L1 expression of 1% or moreprimaryBajorin 202174.5% at 6 mo55.7% at 6 moHR 0.55P<0.001The abstract gives a 98.72% confidence interval of 0.35 to 0.85 (not a 95% interval). The 6-month values are the percentages alive and disease-free.
Survival free from recurrence outside the urothelial tractprimaryBajorin 2021median 22.9 months (19.2–33.4); 77% at 6 momedian 13.7 months (8.4–20.3); 62.7% at 6 moHR 0.72 (95% CI 0.59–0.89)Secondary end point. Hazard ratio for recurrence outside the urothelial tract or death.
Survival free from recurrence outside the urothelial tractPatients with tumour PD-L1 expression of 1% or moreprimaryBajorin 202175.3% at 6 mo56.7% at 6 moHR 0.55 (95% CI 0.39–0.79)Secondary end point.
Results reported for CheckMate 274
EndpointAnalysisNivolumabPlaceboEffect
DFSprimaryBajorin 2021median 20.8 months (16.5–27.6); 74.9% at 6 momedian 10.8 months (8.3–13.9); 60.3% at 6 moHR 0.7P<0.001Hazard ratio for disease recurrence or death; the abstract gives a 98.22% confidence interval of 0.55 to 0.90 (not a 95% interval). The 6-month values are the percentages alive and disease-free.
DFSPatients with tumour PD-L1 expression of 1% or moreprimaryBajorin 202174.5% at 6 mo55.7% at 6 moHR 0.55P<0.001The abstract gives a 98.72% confidence interval of 0.35 to 0.85 (not a 95% interval). The 6-month values are the percentages alive and disease-free.
Survival free from recurrence outside the urothelial tractprimaryBajorin 2021median 22.9 months (19.2–33.4); 77% at 6 momedian 13.7 months (8.4–20.3); 62.7% at 6 moHR 0.72 (95% CI 0.59–0.89)Secondary end point. Hazard ratio for recurrence outside the urothelial tract or death.
Survival free from recurrence outside the urothelial tractPatients with tumour PD-L1 expression of 1% or moreprimaryBajorin 202175.3% at 6 mo56.7% at 6 moHR 0.55 (95% CI 0.39–0.79)Secondary end point.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
Survival free from recurrence outside the urothelial tractSurvival free from recurrence outside the urothelial tract0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
Survival free from recurrence outside the urothelial tract0.720.59–0.89
Survival free from recurrence outside the urothelial tract0.550.39–0.79
Illustrative — modelled from reported values, not trial data. DFS, primary.
0%25%50%75%100%01020304050Months (modelled)
  • Placebo (control)
  • Nivolumab (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsPlaceboNivolumab
0100.0%100.0%
1343.4%64.8%
2618.8%42.0%
398.2%27.3%
523.6%17.7%
Illustrative — modelled from reported values, not trial data. Survival free from recurrence outside the urothelial tract, primary.
0%25%50%75%100%01020304050Months (modelled)
  • Placebo (control)
  • Nivolumab (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsPlaceboNivolumab
0100.0%100.0%
1449.2%65.5%
2923.1%41.6%
4311.4%27.2%
575.6%17.8%
Primary publication: Bajorin DF, Witjes JA, Gschwend JE, Schenker M, Valderrama BP, Tomita Y, et al. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2021;384(22):2102-2114. PubMedDOI

Appears in

Sources

  1. Bajorin DF, Witjes JA, Gschwend JE, Schenker M, Valderrama BP, Tomita Y, et al. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2021;384(22):2102-2114.

    PubMedDOI