Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Endometrial Neoplasms
/ drug therapy
Female
Humans
Middle Aged
Phenylurea Compounds
/ administration & dosage
Quinolines
/ administration & dosage
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:
03 02 2022
03 02 2022
Historique:
pubmed:
20
1
2022
medline:
17
2
2022
entrez:
19
1
2022
Statut:
ppublish
Résumé
Standard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear. In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician's choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival. The end points were evaluated in patients with mismatch repair-proficient (pMMR) disease and in all patients. Safety was also assessed. A total of 827 patients (697 with pMMR disease and 130 with mismatch repair-deficient disease) were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 6.6 vs. 3.8 months; hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.50 to 0.72; P<0.001; overall: 7.2 vs. 3.8 months; hazard ratio, 0.56; 95% CI, 0.47 to 0.66; P<0.001). The median overall survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 17.4 vs. 12.0 months; hazard ratio for death, 0.68; 95% CI, 0.56 to 0.84; P<0.001; overall: 18.3 vs. 11.4 months; hazard ratio, 0.62; 95% CI, 0.51 to 0.75; P<0.001). Adverse events of grade 3 or higher occurred in 88.9% of the patients who received lenvatinib plus pembrolizumab and in 72.7% of those who received chemotherapy. Lenvatinib plus pembrolizumab led to significantly longer progression-free survival and overall survival than chemotherapy among patients with advanced endometrial cancer. (Funded by Eisai and Merck Sharp and Dohme [a subsidiary of Merck]; Study 309-KEYNOTE-775 ClinicalTrials.gov number, NCT03517449.).
Sections du résumé
BACKGROUND
Standard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear.
METHODS
In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician's choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival. The end points were evaluated in patients with mismatch repair-proficient (pMMR) disease and in all patients. Safety was also assessed.
RESULTS
A total of 827 patients (697 with pMMR disease and 130 with mismatch repair-deficient disease) were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 6.6 vs. 3.8 months; hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.50 to 0.72; P<0.001; overall: 7.2 vs. 3.8 months; hazard ratio, 0.56; 95% CI, 0.47 to 0.66; P<0.001). The median overall survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 17.4 vs. 12.0 months; hazard ratio for death, 0.68; 95% CI, 0.56 to 0.84; P<0.001; overall: 18.3 vs. 11.4 months; hazard ratio, 0.62; 95% CI, 0.51 to 0.75; P<0.001). Adverse events of grade 3 or higher occurred in 88.9% of the patients who received lenvatinib plus pembrolizumab and in 72.7% of those who received chemotherapy.
CONCLUSIONS
Lenvatinib plus pembrolizumab led to significantly longer progression-free survival and overall survival than chemotherapy among patients with advanced endometrial cancer. (Funded by Eisai and Merck Sharp and Dohme [a subsidiary of Merck]; Study 309-KEYNOTE-775 ClinicalTrials.gov number, NCT03517449.).
Identifiants
pubmed: 35045221
doi: 10.1056/NEJMoa2108330
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Phenylurea Compounds
0
Quinolines
0
pembrolizumab
DPT0O3T46P
lenvatinib
EE083865G2
Banques de données
ClinicalTrials.gov
['NCT03517449']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
437-448Investigateurs
Gonzalo Gomez Abuin
(G)
Mirta S Varela
(MS)
Maria Valeria Caceres
(MV)
Mauro Orlando
(M)
Pablo Hugo Capellino
(PH)
Diego Lucas Kaen
(DL)
Juan Cundom
(J)
Margarita Sonia Alfie
(MS)
Linda Mileshkin
(L)
Jeffrey Goh
(J)
Andrew Dean
(A)
Sally Baron-Hay
(S)
Ruffo de Freitas
(R)
Fernanda Bronzon Damian
(F)
Angélica Nogueira Rodrigues
(A)
Patrícia Medeiros Milhomem Beato
(P)
Pedro Emanuel Rubini Liedke
(PE)
Andréia Cristina de Melo
(AC)
Maria Del Pilar Estevez Diz
(M)
Roberto Hegg
(R)
Diane Provencher
(D)
Helen MacKay
(H)
Stephen Welch
(S)
Prafull Ghatage
(P)
Susie Kit Sze Lau
(SKS)
Alexandra Sebastianelli
(A)
Suzanne Fortin
(S)
Shaundra Popowich
(S)
Paul Bessette
(P)
Johanne Weberpals
(J)
Amit Oza
(A)
Edwin Alberto Hoyos
(EA)
Andres Yepes
(A)
Tomas Sanchez
(T)
Luis Leonardo Rojas
(LL)
Jorge Salinas
(J)
Marc Edy Pierre
(ME)
Juan Guillermo Restrepo
(JG)
Oscar Madiedo
(O)
Ivan José Bustillo
(IJ)
Frederic Selle
(F)
Emeline Colomba
(E)
Isabelle Ray-Coquard
(I)
Michel Fabbro
(M)
Anne Floquet
(A)
Annick Chevalier-Place
(A)
Cyril Abdeddaim
(C)
Thibault de la Motte Rouge
(T)
Florence Joly-Lobbedez
(F)
Alain Lortholary
(A)
Benoit You
(B)
Jerome Alexandre
(J)
Anne-Claire Hardy-Bessard
(AC)
Alexander Hein
(A)
Pauline Wimberger
(P)
Jalid Sehouli
(J)
Andreas Hartkopf
(A)
Barbara Schmalfeldt
(B)
Austin Duffy
(A)
Catherine Margaret Kelly
(CM)
Ronnie Shapira
(R)
Frommer Frommer
(F)
Ram Eitan
(R)
Amnon Amit
(A)
Talia Levy
(T)
Mihai Meirovitz
(M)
Amichay Meirovitz
(A)
Giorgia Mangili
(G)
Paolo Scollo
(P)
Domenica Lorusso
(D)
Francesco Raspagliesi
(F)
Carmela Pisano
(C)
Ugo de Giorgi
(U)
Nicoletta Colombo
(N)
Giovanni Scambia
(G)
Kosei Hasegawa
(K)
Yasuyuki Hirashima
(Y)
Takayuki Enomoto
(T)
Hiroaki Itamochi
(H)
Kimio Ushijima
(K)
Aikou Okamoto
(A)
Kazuhiro Takehara
(K)
Koji Matsumoto
(K)
Mika Mizuno
(M)
Jun Sakata
(J)
Wataru Yamagami
(W)
Shinichiro Minobe
(S)
Kan Yonemori
(K)
Nobuhiro Takeshima
(N)
Mayu Yunokawa
(M)
Hideki Tokunaga
(H)
Takashi Matsumoto
(T)
Hiroaki Kobayashi
(H)
Toyomi Satoh
(T)
Hirokuni Takano
(H)
Masae Ikeda
(M)
Ángel Gómez Villanueva
(Á)
Juan Paulo Ceja García
(JP)
Jorge Luis Martínez Rodríguez
(JL)
Erika Castillo
(E)
María de la Luz García
(M)
Michelle Wilson
(M)
Rafal Tarnawski
(R)
Iwona Glogowska
(I)
Mariusz Bidzinski
(M)
Joanna Pikiel
(J)
Malgorzata Okreglicka Lewandowska
(M)
Igor Jacek Symonowicz
(I)
Anna Danska-Bidzinska
(A)
Aneta Cymbaluk-Ploska
(A)
Pavel Igorevich Skopin
(P)
Alla Sergeevna Lisyanskaya
(AS)
Alfiya Irekovna Khasanova
(AI)
Sergey Alexandrovich Lazarev
(SA)
Larisa Aleksandrovna Kolomiets
(LA)
Alexander Alexandrovich Fedenko
(AA)
Oleg Nikolaevich Lipatov
(ON)
Olga Nikolaevna Mikheeva
(ON)
Anna Genrikhovna Kedrova
(AG)
Sang Yoon Park
(SY)
Myong Cheol Lim
(MC)
Jae-Weon Kim
(JW)
Yong Man Kim
(YM)
Byoung-Gie Kim
(BG)
Ana Oaknin Benzaquen
(A)
Marta Gil Martín
(M)
José Ángel Arranz Arija
(JÁ)
Eva María Guerra Alía
(EM)
Antonio Casado Herráez
(A)
Antonio González Martín
(A)
Ana Santaballa Bertrán
(A)
Peng-Hui Wang
(PH)
Wen-Fang Cheng
(WF)
Chien-Hsing Lu
(CH)
Chen-Hsuan Wu
(CH)
Chih-Long Chang
(CL)
Jian-Tai Qiu
(JT)
Ting-Chang Chang
(TC)
Wen-Shiung Liou
(WS)
Ozden Altundag
(O)
Zafer Arik
(Z)
Bulent Orhan
(B)
Hatice Doruk
(H)
Ozkan Kanat
(O)
Ali Arican
(A)
Cetin Ordu
(C)
Huseyin Mertsoylu
(H)
Ulus Ali Sanli
(UA)
Jonathan Krell
(J)
Christine Parkinson
(C)
Susana Banerjee
(S)
Mary McCormack
(M)
Clare Green
(C)
Melanie Powell
(M)
Rebecca Herbertson
(R)
James Wilson
(J)
Ana Montes
(A)
Rebecca Kristeleit
(R)
Robert W Holloway
(RW)
Maria Bell
(M)
Paul Celano
(P)
Edwin Alvarez
(E)
Adam ElNaggar
(A)
Agustin A Garcia
(AA)
Sharad Ghamande
(S)
Deena M Graham
(DM)
Mary Tilley Jenkins Vogel
(M)
Stephan DiSean Kendall
(SD)
Gottfried E Konecny
(GE)
Sharyn Lewin
(S)
David Scott Miller
(DS)
Debra L Richardson
(DL)
Richard G Moore
(RG)
David R Spriggs
(DR)
Angeles Secord
(A)
Brian Slomovitz
(B)
Jonathan Trent
(J)
Alessandro Santin
(A)
Vicky Makker
(V)
Cheryl A Aylesworth
(CA)
Charles Anderson
(C)
Joseph de la Garza
(J)
Bradley Monk
(B)
Lynne Knowles
(L)
Commentaires et corrections
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