Adjuvant nivolumab (NIVO) vs placebo (PBO) for high-risk muscle-invasive urothelial carcinoma (MIUC): Additional efficacy outcomes including overall survival (OS) in patients (pts) with muscle-invasive bladder cancer (MIBC) from CheckMate 274.
Authors: Milowsky Matthew I. , Galsky Matthew D. , Witjes Johannes Alfred , Gschwend Jürgen E. , Schenker Michael , Perez Valderrama Begona , Tomita Yoshihiko , Bamias Aristotelis , Lebret Thierry , Shariat Shahrokh F. , Park Se Hoon , Agerbaek Mads , Jha Gautam Gopalji , Stenner Frank , Ye Dingwei , Giudici Fabio , Connors Jessica , Zhang Joshua , Bajorin Dean F. 
Published: February 2025

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Background:
In the phase 3, randomized, double-blind CheckMate 274 trial, adjuvant NIVO demonstrated statistically signiﬁcant and clinically meaningful disease-free survival (DFS) beneﬁt vs PBO in pts with high-risk MIUC after radical surgery (RS) ± prior neoadjuvant cisplatin-based chemotherapy (NAC). With extended 3-y median follow-up, continued improvements in DFS were seen with NIVO vs PBO in the primary efficacy populations (intent-to-treat [ITT], tumor programmed death ligand 1 [PD-L1] expression ≥ 1%) and in pts with MIBC. Early trends in interim OS favored NIVO vs PBO in ITT and tumor PD-L1 ≥ 1% pts. Here we report additional efficacy outcomes for pts with MIBC.
Methods:
Pts were randomized 1:1 to NIVO 240 mg every 2 wk or PBO for ≤ 1 y of adjuvant treatment, stratified by tumor PD-L1 expression, nodal status, and prior NAC. Primary endpoints were DFS in ITT and tumor PD-L1 expression ≥ 1% pts. OS in ITT and PD-L1 ≥ 1% pts was a secondary endpoint. Analysis of MIBC pts was exploratory. MIBC OS data are from preplanned interim analyses of ITT and PD-L1 ≥ 1% pts. OS follow-up is ongoing as the prespecified statistical boundaries for significance in ITT and PD-L1 ≥ 1% pts were not crossed at the time of these analyses.
Results:
Of 709 randomized pts (ITT), 560 (79%) had MIBC (NIVO, n = 279; PBO, n = 281); 284 (51%) of MIBC pts had prior NAC. With median follow-up of 36.1 mo (ITT), DFS improvement with NIVO vs PBO was consistent between all pts with MIBC (hazard ratio [HR] 0.63) and those with (HR 0.58) and without prior NAC (HR 0.69; Table). For OS, HRs favored NIVO vs PBO in all pts with MIBC (HR 0.70) and the tumor PD-L1 ≥ 1% subgroup (HR 0.48), as well as in pts with MIBC with (HR 0.74) and without prior NAC (HR 0.67). Safety was consistent with previous data in ITT pts; no new safety signals were identified.
Conclusions:
With 3-y median follow-up, consistent benefit in DFS was observed with NIVO vs PBO in all MIBC pts and across prior NAC subgroups. The HR for OS favored NIVO in all MIBC pts, in those with PD-L1 ≥ 1%, and regardless of prior NAC status. These results continue to support adjuvant NIVO as a standard of care for high-risk MIUC and MIBC, potentially providing an opportunity for a curative outcome. Clinical trial information:
NCT02632409
.

NIVOn
NIVOMedian(95% CI), mo
PBOn
PBOMedian(95% CI), mo
HR (95% CI)

DFS

All MIBC

279
25.6 (19.2–41.8)
281
8.5 (7.3–13.7)
0.63 (0.51–0.78)

With prior NAC
142
19.6 (15.6–48.2)
142
8.3 (5.6–11.2)
0.58 (0.43–0.79)

No prior NAC
137
25.9 (19.2–51.5)
139
13.7 (7.8–22.1)
0.69 (0.50–0.94)

OS

All MIBC

279
NR (45.0–NE)
281
39.9 (29.8–52.1)
0.70 (0.55–0.90)

PD-L1 ≥ 1%
113
NR (NE–NE)
117
37.6 (26.9–NE)
0.48 (0.29–0.77)

With prior NAC
142
55.2 (41.8–NE)
142
40.2 (28.8–53.7)
0.74 (0.53–1.03)

No prior NAC
137
NR (40.7–NE)
139
37.7 (28.7–65.2)
0.67 (0.47–0.95)

NE, not estimable; NR, not reached.