Survival with Cemiplimab in Recurrent Cervical Cancer.
Adenocarcinoma
/ drug therapy
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ adverse effects
Antineoplastic Agents, Immunological
/ adverse effects
Biomarkers, Tumor
/ metabolism
Carcinoma, Adenosquamous
/ drug therapy
Disease Progression
Female
Humans
Middle Aged
Neoplasm Recurrence, Local
/ drug therapy
Programmed Cell Death 1 Receptor
/ metabolism
Quality of Life
Survival Analysis
Uterine Cervical Neoplasms
/ drug therapy
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:
10 02 2022
10 02 2022
Historique:
entrez:
9
2
2022
pubmed:
10
2
2022
medline:
19
2
2022
Statut:
ppublish
Résumé
Patients with recurrent cervical cancer have a poor prognosis. Cemiplimab, the fully human programmed cell death 1 (PD-1)-blocking antibody approved to treat lung and skin cancers, has been shown to have preliminary clinical activity in this population. In this phase 3 trial, we enrolled patients who had disease progression after first-line platinum-containing chemotherapy, regardless of their programmed cell death ligand 1 (PD-L1) status. Women were randomly assigned (1:1) to receive cemiplimab (350 mg every 3 weeks) or the investigator's choice of single-agent chemotherapy. The primary end point was overall survival. Progression-free survival and safety were also assessed. A total of 608 women were enrolled (304 in each group). In the overall trial population, median overall survival was longer in the cemiplimab group than in the chemotherapy group (12.0 months vs. 8.5 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.84; two-sided P<0.001). The overall survival benefit was consistent in both histologic subgroups (squamous-cell carcinoma and adenocarcinoma [including adenosquamous carcinoma]). Progression-free survival was also longer in the cemiplimab group than in the chemotherapy group in the overall population (hazard ratio for disease progression or death, 0.75; 95% CI, 0.63 to 0.89; two-sided P<0.001). In the overall population, an objective response occurred in 16.4% (95% CI, 12.5 to 21.1) of the patients in the cemiplimab group, as compared with 6.3% (95% CI, 3.8 to 9.6) in the chemotherapy group. An objective response occurred in 18% (95% CI, 11 to 28) of the cemiplimab-treated patients with PD-L1 expression greater than or equal to 1% and in 11% (95% CI, 4 to 25) of those with PD-L1 expression of less than 1%. Overall, grade 3 or higher adverse events occurred in 45.0% of the patients who received cemiplimab and in 53.4% of those who received chemotherapy. Survival was significantly longer with cemiplimab than with single-agent chemotherapy among patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. (Funded by Regeneron Pharmaceuticals and Sanofi; EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 ClinicalTrials.gov number, NCT03257267.).
Sections du résumé
BACKGROUND
Patients with recurrent cervical cancer have a poor prognosis. Cemiplimab, the fully human programmed cell death 1 (PD-1)-blocking antibody approved to treat lung and skin cancers, has been shown to have preliminary clinical activity in this population.
METHODS
In this phase 3 trial, we enrolled patients who had disease progression after first-line platinum-containing chemotherapy, regardless of their programmed cell death ligand 1 (PD-L1) status. Women were randomly assigned (1:1) to receive cemiplimab (350 mg every 3 weeks) or the investigator's choice of single-agent chemotherapy. The primary end point was overall survival. Progression-free survival and safety were also assessed.
RESULTS
A total of 608 women were enrolled (304 in each group). In the overall trial population, median overall survival was longer in the cemiplimab group than in the chemotherapy group (12.0 months vs. 8.5 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.84; two-sided P<0.001). The overall survival benefit was consistent in both histologic subgroups (squamous-cell carcinoma and adenocarcinoma [including adenosquamous carcinoma]). Progression-free survival was also longer in the cemiplimab group than in the chemotherapy group in the overall population (hazard ratio for disease progression or death, 0.75; 95% CI, 0.63 to 0.89; two-sided P<0.001). In the overall population, an objective response occurred in 16.4% (95% CI, 12.5 to 21.1) of the patients in the cemiplimab group, as compared with 6.3% (95% CI, 3.8 to 9.6) in the chemotherapy group. An objective response occurred in 18% (95% CI, 11 to 28) of the cemiplimab-treated patients with PD-L1 expression greater than or equal to 1% and in 11% (95% CI, 4 to 25) of those with PD-L1 expression of less than 1%. Overall, grade 3 or higher adverse events occurred in 45.0% of the patients who received cemiplimab and in 53.4% of those who received chemotherapy.
CONCLUSIONS
Survival was significantly longer with cemiplimab than with single-agent chemotherapy among patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. (Funded by Regeneron Pharmaceuticals and Sanofi; EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 ClinicalTrials.gov number, NCT03257267.).
Identifiants
pubmed: 35139273
doi: 10.1056/NEJMoa2112187
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
Biomarkers, Tumor
0
Programmed Cell Death 1 Receptor
0
cemiplimab
6QVL057INT
Banques de données
ClinicalTrials.gov
['NCT03257267']
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
544-555Investigateurs
Danny Rischin
(D)
Chee Lee
(C)
Jeffrey Goh
(J)
Andrew Dean
(A)
Ratnesh Srivastav
(R)
Jean Francois Baurain
(JF)
Maryam Bourhaba
(M)
Frederic Kridelka
(F)
Ignace Vergote
(I)
Greet Huygh
(G)
Laura Polastro
(L)
Daniella Ramone
(D)
Giuliano Santos Borges
(G)
Andrea Juliana Pereira De Santana Gomes
(AJ)
Rodrigo Pereira
(R)
Paulo Alexandre Ribiero Mora
(PA)
Fernanda Bronzon Damian
(FB)
Andreia Cristina de Melo
(AC)
Andre Borba Reiriz
(AB)
Stephen Welch
(S)
Susie Lau
(S)
Anna Tinker
(A)
Vanessa Samouëlian
(V)
Prafull Ghatage
(P)
Stephanie L'Heureux
(S)
Suzanne Fortin
(S)
Flora Zagouri
(F)
George Fountzilas
(G)
Athina Christopoulou
(A)
Antonio Ardizzoia
(A)
Claudio Zamagni
(C)
Graziana Ronzino
(G)
Antonella Savarese
(A)
Nicoletta Colombo
(N)
Ugo de Giorgi
(U)
Domenica Lorusso
(D)
Kosei Hasegawa
(K)
Yoichi Aoki
(Y)
Masao Okadome
(M)
Nao Suzuki
(N)
Hidemichi Watari
(H)
Kazuhiro Takehara
(K)
Yoichi Kobayashi
(Y)
Takashi Matsumoto
(T)
Kimio Ushijima
(K)
Yoshio Yoshida
(Y)
Kan Yonemori
(K)
Harushige Yokota
(H)
Shunji Takahashi
(S)
Beata Maćkowiak-Matejczyk
(B)
Rafal Tarnawski
(R)
Joanna Pikiel
(J)
Andrzej Roszak
(A)
Dariusz Kieszko
(D)
Alla Lisyanskaya
(A)
Nadezhda Mikhaylova
(N)
Mikhail Uvarov
(M)
Eduard Pshevlotskiy
(E)
Yulia Makarova
(Y)
Vadim Shirinkin
(V)
Evgeniy A Gotovkin
(EA)
Mikhail Osipov
(M)
Jae-Kwan Lee
(JK)
Chi-Heum Cho
(CH)
Jae-Hoon Kim
(JH)
Myong Cheol Lim
(MC)
Yong Man Kim
(YM)
Hee Seung Kim
(HS)
Ana Benzaquen Oaknin
(A)
Ignacio Romero Romero
(I)
Pilar Barretina Ginesta
(P)
Jesus Garcia-Donas Jimenez
(J)
Eva Maria Guerra Alía
(EM)
Alfonso Yubero-Esteban
(A)
Maria Jesus Rubio Perez
(MJ)
Maria Jose Bermejo Perez
(MJ)
Jesus Damian Alarcon Company
(JD)
Ana Santaballa Bertran
(A)
Chien-Hsing Lu
(CH)
Peng-Hui Wang
(PH)
Chih-Long Chang
(CL)
Chi-Feng Chung
(CF)
Mary McCormack
(M)
Anjana Anand
(A)
John Liao
(J)
Veena John
(V)
Lisa Nicole Abaid
(LN)
Marcia Hernandez
(M)
Scott Richard
(S)
Michael J Sundborg
(MJ)
Katrina Wade
(K)
Leslie Boyd
(L)
Bradley J Monk
(BJ)
Helena D Eshed
(HD)
Krishnansu S Tewari
(KS)
Joseph Buscema
(J)
David A Fishman
(DA)
Masanobu Nakajima
(M)
Masaki Nakamura
(M)
Kosuke Narumiya
(K)
Tomohiro Nishina
(T)
Takashi Ogata
(T)
Hitoshi Ojima
(H)
Toshiyasu Ojima
(T)
Morihito Okada
(M)
Eiji Oki
(E)
Ken Sasaki
(K)
Atsushi Sato
(A)
Hideaki Shimada
(H)
Yoshifumi Suga
(Y)
Koichi Takagi
(K)
Masanobu Takahashi
(M)
Keisei Taku
(K)
Masahiro Tsuda
(M)
Kunihiro Tsuji
(K)
Takahiro Tsushima
(T)
Masaki Ueno
(M)
Yoshiyuki Yamaguchi
(Y)
Hisateru Yasui
(H)
Kazuhiro Yoshida
(K)
Young Jin Choi
(YJ)
Jin-Hyoung Kang
(JH)
Jong Gwang Kim
(JG)
Hye Ryun Kim
(HR)
Sung-Bae Kim
(SB)
Yeul Hong Kim
(YH)
Jong-Seok Lee
(JS)
Young Joo Min
(YJ)
Im Il Na
(II)
Sang Cheul Oh
(SC)
Eun-Kee Song
(EK)
Jong-Mu Sun
(JM)
Hwan Jung Yun
(HJ)
Francisco Gutierrez-Delgado
(F)
Pedro Martinez Figueroa
(P)
Alejandro Molina Alavez
(A)
German Calderillo Ruiz
(G)
Alejandro Figueroa
(A)
Paola Montenegro
(P)
Jose Carlos Revilla
(JC)
Tomasz Skoczylas
(T)
Lucjan S Wyrwicz
(LS)
Doina Elena Ganea
(DE)
Ingrid Adriana Iordan
(IA)
Anca C Mihailov
(AC)
Michael Schenker
(M)
Nina Alexeevna Karaseva
(NA)
Elena V Poddubskaya
(EV)
Chau Hsien Matthew Ng
(CHM)
Wei-Peng Yong Maria Alsina
(WYM)
Paloma Peinado
(P)
Ming-Huang Chen
(MH)
Yin-Hsun Feng
(YH)
Ming-Mo Hou
(MM)
Chih-Hung Hsu
(CH)
Shau-Hsuan Li
(SH)
Chen-Yuan Lin
(CY)
Cheng-Hsu Wang
(CH)
Chuan-Cheng Wang
(CC)
Tsang-En Wang
(TE)
I-Chen Wu
(IC)
Wen-Chi Yang
(WC)
Chia-Jui Yen
(CJ)
Irfan Cicin
(I)
Muhammet Ali A Kaplan
(MAA)
Dogan Uncu
(D)
John Bridgewater
(J)
Ian Chau
(I)
Nikolaos Diamantis
(N)
Wasat Mansoor
(W)
Ghulam Abbas
(G)
Santiago Aparo
(S)
Mariela Blum Murphy
(M)
Allen L Cohn
(AL)
Joseph Anthony Fiorillo
(JA)
Mark D Kochenderfer
(MD)
Steven L McCune
(SL)
Rutika Jitesh Mehta
(RJ)
Andrew Scott Paulson
(AS)
Nabil F Saba
(NF)
Spencer H Shao
(SH)
Rachna T Shroff
(RT)
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