Τίτλος:
Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial
Carcinoma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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, .)
Συγγραφείς:
Bajorin, D. F.
Witjes, J. A.
Gschwend, J. E.
Schenker, M.
and Valderrama, B. P.
Tomita, Y.
Bamias, A.
Lebret, T. and
Shariat, S. F.
Park, S. H.
Ye, D.
Agerbaek, M.
Enting,
D.
McDermott, R.
Gajate, P.
Peer, A.
Milowsky, I, M. and
Nosov, A.
Antonio Jr, J. N.
Tupikowski, K.
Toms, L. and
Fischer, B. S.
Qureshi, A.
Collette, S.
Unsal-Kacmaz, K. and
Broughton, E.
Zardavas, D.
Koon, H. B.
Galsky, M. D.
Περιοδικό:
The New England journal of medicine
Εκδότης:
MASSACHUSETTS MEDICAL SOC
DOI:
10.1056/NEJMoa2034442
