Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ adverse effects
Antineoplastic Agents, Immunological
/ adverse effects
Carcinoma, Renal Cell
/ drug therapy
Chemotherapy, Adjuvant
/ adverse effects
Disease-Free Survival
Double-Blind Method
Female
Humans
Intention to Treat Analysis
Kidney Neoplasms
/ drug therapy
Male
Middle Aged
Nephrectomy
Recurrence
Survival Analysis
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
19 08 2021
19 08 2021
Historique:
entrez:
18
8
2021
pubmed:
19
8
2021
medline:
26
8
2021
Statut:
ppublish
Résumé
Patients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence. In a double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with clear-cell renal-cell carcinoma who were at high risk for recurrence after nephrectomy, with or without metastasectomy, to receive either adjuvant pembrolizumab (at a dose of 200 mg) or placebo intravenously once every 3 weeks for up to 17 cycles (approximately 1 year). The primary end point was disease-free survival according to the investigator's assessment. Overall survival was a key secondary end point. Safety was a secondary end point. A total of 496 patients were randomly assigned to receive pembrolizumab, and 498 to receive placebo. At the prespecified interim analysis, the median time from randomization to the data-cutoff date was 24.1 months. Pembrolizumab therapy was associated with significantly longer disease-free survival than placebo (disease-free survival at 24 months, 77.3% vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval [CI], 0.53 to 0.87; P = 0.002 [two-sided]). The estimated percentage of patients who remained alive at 24 months was 96.6% in the pembrolizumab group and 93.5% in the placebo group (hazard ratio for death, 0.54; 95% CI, 0.30 to 0.96). Grade 3 or higher adverse events of any cause occurred in 32.4% of the patients who received pembrolizumab and in 17.7% of those who received placebo. No deaths related to pembrolizumab therapy occurred. Pembrolizumab treatment led to a significant improvement in disease-free survival as compared with placebo after surgery among patients with kidney cancer who were at high risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.).
Sections du résumé
BACKGROUND
Patients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence.
METHODS
In a double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with clear-cell renal-cell carcinoma who were at high risk for recurrence after nephrectomy, with or without metastasectomy, to receive either adjuvant pembrolizumab (at a dose of 200 mg) or placebo intravenously once every 3 weeks for up to 17 cycles (approximately 1 year). The primary end point was disease-free survival according to the investigator's assessment. Overall survival was a key secondary end point. Safety was a secondary end point.
RESULTS
A total of 496 patients were randomly assigned to receive pembrolizumab, and 498 to receive placebo. At the prespecified interim analysis, the median time from randomization to the data-cutoff date was 24.1 months. Pembrolizumab therapy was associated with significantly longer disease-free survival than placebo (disease-free survival at 24 months, 77.3% vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval [CI], 0.53 to 0.87; P = 0.002 [two-sided]). The estimated percentage of patients who remained alive at 24 months was 96.6% in the pembrolizumab group and 93.5% in the placebo group (hazard ratio for death, 0.54; 95% CI, 0.30 to 0.96). Grade 3 or higher adverse events of any cause occurred in 32.4% of the patients who received pembrolizumab and in 17.7% of those who received placebo. No deaths related to pembrolizumab therapy occurred.
CONCLUSIONS
Pembrolizumab treatment led to a significant improvement in disease-free survival as compared with placebo after surgery among patients with kidney cancer who were at high risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.).
Identifiants
pubmed: 34407342
doi: 10.1056/NEJMoa2106391
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
pembrolizumab
DPT0O3T46P
Banques de données
ClinicalTrials.gov
['NCT03142334']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
683-694Subventions
Organisme : NCI NIH HHS
ID : P50 CA101942
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006516
Pays : United States
Investigateurs
Luis Enrique Fein
(LE)
Diego Lucas Kaen
(DL)
Ruben Dario Kowalyszyn
(RD)
Alejandro Dri
(A)
Juan Pablo Sade
(JP)
Marcelo Daniel Tatangelo
(MD)
Juan Jose Zarba
(JJ)
Viviana Elizabeth Leiva
(VE)
Guillermo Ariel Mendez
(GA)
Margarita Sonia Alfie
(MS)
Howard Paul Gurney
(HP)
Ian D Davis
(ID)
Thomas R Ferguson
(TR)
Muhammad Khattak
(M)
Francis Parnis
(F)
Mark Warren
(M)
Samuel John Harris
(SJ)
Stephen John Brown
(SJ)
Carole Harris
(C)
Juliana de Janoski Menezes
(J)
Andre Poisl Fay
(AP)
Joao Neif Antonio Junior
(JNA)
Rita de Cassia Costamilan
(R)
Patricia Medeiros Milhomem Beato
(P)
Roberto Odebrecht Rocha
(R)
David Muniz
(D)
Adriano Goncalves E Silva
(A)
Silvio Correia Sales
(S)
Fernando Maciel Barbosa
(F)
Jussaine Silva
(J)
Leandro Brust
(L)
Liane Rapatoni
(L)
Genevieve Faucher
(G)
Nayyer Iqbal
(N)
Skander Ghedira
(S)
Eric W Winquist
(EW)
Gregory Lo
(G)
Carrie Yeung
(C)
Nadine Martel
(N)
Daniele Marceau
(D)
Jean-Benoit Paradis
(JB)
Henry Jacob Conter
(HJ)
Muhammad Salim
(M)
Aly-Khan Lalani
(AK)
Nawar Hanna
(N)
Vamsee Torri
(V)
Jeffrey Graham
(J)
Michael Levesque
(M)
Alejandro Acevedo
(A)
Francisco Orlandi
(F)
Christian Caglevic
(C)
Jose Luis Leal
(JL)
Mauricio Mahave
(M)
Carolina Ibanez
(C)
Luis Villanueva
(L)
Maria Alejandra Ojeda
(MA)
Pedro Galaz
(P)
Plinio Fernandez
(P)
Patricia Carvajal
(P)
Francisco Flores
(F)
Eduardo Yanez Ruiz
(E)
Angela Estay
(A)
Gustavo Adolfo Rojas-Uribe
(GA)
Manuel Enrique Gonzalez Fernandez
(ME)
Juan Camilo Ospina
(JC)
Carmen Marcela Alcala Castro
(CM)
Isabel Cristina Durango
(IC)
Juan Andres Rubiano
(JA)
Andres Felipe Cardona
(AF)
Ray Manneh
(R)
Zdenek Kral
(Z)
Bohuslav Melichar
(B)
Petra Holeckova
(P)
Jana Prausova
(J)
Tomas Buchler
(T)
Hana Perkova
(H)
Rostislav Kotasek
(R)
Jaroslav Hajek
(J)
Petri Bono
(P)
Katriina Peltola
(K)
Krista Kankaanranta
(K)
Pirkko-Liisa Kellokumpu-Lehtinen
(PL)
Peter Bostrom
(P)
Juha Kononen
(J)
Heikki Hakkarainen
(H)
Hanna Ronkainen
(H)
Antoine Thiery-Vuillemin
(A)
Christine Chevreau
(C)
Marine Gross-Goupil
(M)
Delphine Topart
(D)
Jean Laurent Deville
(JL)
Stephane Oudard
(S)
Frederic Rolland
(F)
Sophie Abadie-Lacourtoisie
(S)
Brigitte Laguerre
(B)
Delphine Borchiellini
(D)
Sophie Tartas
(S)
Jens Bedke
(J)
Peter J Goebell
(PJ)
Marc-Oliver Grimm
(MO)
Anja Lorch
(A)
Axel Merseburger
(A)
Stefan Hauser
(S)
Christian Thomas
(C)
Thomas Hoefner
(T)
Manfred Wirth
(M)
Susan Feyerabend
(S)
Christian Niedworok
(C)
Andrej Panic
(A)
Heinz Kirchen
(H)
Andreas Neisius
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Michael Rink
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(F)
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(W)
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Masafumi Oyama
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(H)
Hideyasu Matsuyama
(H)
Yoshiaki Yamamoto
(Y)
Ryuichi Mizuno
(R)
Hirotsugu Uemura
(H)
Masatoshi Eto
(M)
Satoshi Anai
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Masao Tsujihata
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Hiroyuki Tsunemori
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Yoshihiko Tomita
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Naoya Masumori
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Toshimi Takano
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Yuji Miura
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Satoshi Tamada
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Naoto Sassa
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Hans Westgeest
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Paul Hamberg
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(J)
Piotr Sawrycki
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Boguslawa Karaszewska
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Ewa Maria Nowakowska-Zajdel
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Dariusz Sawka
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(B)
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(R)
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(A)
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(A)
Michail Iosifovich Shkolnik
(M)
Vzevolod Borisovich Matveev
(V)
Sergey G Afanasyev
(SG)
Evgeniy Kopyltsov
(E)
Ruslan Zukov
(R)
Eugeniy Aleksandrovich Fomin
(E)
Oleg Nikolaevich Lipatov
(O)
Jae Lyun Lee
(JL)
Se Hoon Park
(SH)
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(B)
Miso Kim
(M)
Sun Young Rha
(SY)
Jinsoo Chung
(J)
Enrique Grande
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Miguel Angel Climent Duran
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