TY - JOUR
TI - Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial
Carcinoma
AU - Bajorin, D. F.
AU - Witjes, J. A.
AU - Gschwend, J. E.
AU - Schenker, M.
AU - and Valderrama, B. P.
AU - Tomita, Y.
AU - Bamias, A.
AU - Lebret, T. and
AU - Shariat, S. F.
AU - Park, S. H.
AU - Ye, D.
AU - Agerbaek, M.
AU - Enting,
AU - D.
AU - McDermott, R.
AU - Gajate, P.
AU - Peer, A.
AU - Milowsky, I, M. and
AU - Nosov, A.
AU - Antonio Jr, J. N.
AU - Tupikowski, K.
AU - Toms, L. and
AU - Fischer, B. S.
AU - Qureshi, A.
AU - Collette, S.
AU - Unsal-Kacmaz, K. and
AU - Broughton, E.
AU - Zardavas, D.
AU - Koon, H. B.
AU - Galsky, M. D.
JO - The New England journal of medicine
PY - 2021
VL - 384
TODO - 22
SP - 2102-2114
PB - MASSACHUSETTS MEDICAL SOC
SN - null
TODO - 10.1056/NEJMoa2034442
TODO - null
TODO - Adjuvant Nivolumab for Invasive Urothelial Carcinoma
In a prospective, randomized trial involving patients with urothelial
carcinoma who had undergone radical surgery, adjuvant nivolumab was
compared with placebo. The median disease-free survival was 20.8 months
with nivolumab and 10.8 months with placebo. Treatment-related adverse
events of grade 3 or higher were noted in 17.9% of patients in the
nivolumab group.
Background
The role of adjuvant treatment in high-risk muscle-invasive urothelial
carcinoma after radical surgery is not clear.
Methods
In a phase 3, multicenter, double-blind, randomized, controlled trial,
we assigned patients with muscle-invasive urothelial carcinoma who had
undergone radical surgery to receive, in a 1:1 ratio, either nivolumab
(240 mg intravenously) or placebo every 2 weeks for up to 1 year.
Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed.
The primary end points were disease-free survival among all the patients
(intention-to-treat population) and among patients with a tumor
programmed death ligand 1 (PD-L1) expression level of 1% or more.
Survival free from recurrence outside the urothelial tract was a
secondary end point.
Results
A total of 353 patients were assigned to receive nivolumab and 356 to
receive placebo. The median disease-free survival in the
intention-to-treat population was 20.8 months (95% confidence interval
[CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to
13.9) with placebo. The percentage of patients who were alive and
disease-free at 6 months was 74.9% with nivolumab and 60.3% with
placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI,
0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of
1% or more, the percentage of patients was 74.5% and 55.7%,
respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001).
The median survival free from recurrence outside the urothelial tract in
the intention-to-treat population was 22.9 months (95% CI, 19.2 to
33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with
placebo. The percentage of patients who were alive and free from
recurrence outside the urothelial tract at 6 months was 77.0% with
nivolumab and 62.7% with placebo (hazard ratio for recurrence outside
the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among
patients with a PD-L1 expression level of 1% or more, the percentage of
patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95%
CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher
occurred in 17.9% of the nivolumab group and 7.2% of the placebo
group. Two treatment-related deaths due to pneumonitis were noted in the
nivolumab group.
Conclusions
In this trial involving patients with high-risk muscle-invasive
urothelial carcinoma who had undergone radical surgery, disease-free
survival was longer with adjuvant nivolumab than with placebo in the
intention-to-treat population and among patients with a PD-L1 expression
level of 1% or more. (Funded by Bristol Myers Squibb and Ono
Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, .)
ER -