Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma.
Aged
Antibodies, Monoclonal, Humanized
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Bevacizumab
/ administration & dosage
Carcinoma, Hepatocellular
/ drug therapy
Female
Humans
Intention to Treat Analysis
Kaplan-Meier Estimate
Liver Neoplasms
/ drug therapy
Male
Middle Aged
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Quality of Life
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:
14 05 2020
14 05 2020
Historique:
entrez:
14
5
2020
pubmed:
14
5
2020
medline:
23
5
2020
Statut:
ppublish
Résumé
The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinoma. In a global, open-label, phase 3 trial, patients with unresectable hepatocellular carcinoma who had not previously received systemic treatment were randomly assigned in a 2:1 ratio to receive either atezolizumab plus bevacizumab or sorafenib until unacceptable toxic effects occurred or there was a loss of clinical benefit. The coprimary end points were overall survival and progression-free survival in the intention-to-treat population, as assessed at an independent review facility according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). The intention-to-treat population included 336 patients in the atezolizumab-bevacizumab group and 165 patients in the sorafenib group. At the time of the primary analysis (August 29, 2019), the hazard ratio for death with atezolizumab-bevacizumab as compared with sorafenib was 0.58 (95% confidence interval [CI], 0.42 to 0.79; P<0.001). Overall survival at 12 months was 67.2% (95% CI, 61.3 to 73.1) with atezolizumab-bevacizumab and 54.6% (95% CI, 45.2 to 64.0) with sorafenib. Median progression-free survival was 6.8 months (95% CI, 5.7 to 8.3) and 4.3 months (95% CI, 4.0 to 5.6) in the respective groups (hazard ratio for disease progression or death, 0.59; 95% CI, 0.47 to 0.76; P<0.001). Grade 3 or 4 adverse events occurred in 56.5% of 329 patients who received at least one dose of atezolizumab-bevacizumab and in 55.1% of 156 patients who received at least one dose of sorafenib. Grade 3 or 4 hypertension occurred in 15.2% of patients in the atezolizumab-bevacizumab group; however, other high-grade toxic effects were infrequent. In patients with unresectable hepatocellular carcinoma, atezolizumab combined with bevacizumab resulted in better overall and progression-free survival outcomes than sorafenib. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT03434379.).
Sections du résumé
BACKGROUND
The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinoma.
METHODS
In a global, open-label, phase 3 trial, patients with unresectable hepatocellular carcinoma who had not previously received systemic treatment were randomly assigned in a 2:1 ratio to receive either atezolizumab plus bevacizumab or sorafenib until unacceptable toxic effects occurred or there was a loss of clinical benefit. The coprimary end points were overall survival and progression-free survival in the intention-to-treat population, as assessed at an independent review facility according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).
RESULTS
The intention-to-treat population included 336 patients in the atezolizumab-bevacizumab group and 165 patients in the sorafenib group. At the time of the primary analysis (August 29, 2019), the hazard ratio for death with atezolizumab-bevacizumab as compared with sorafenib was 0.58 (95% confidence interval [CI], 0.42 to 0.79; P<0.001). Overall survival at 12 months was 67.2% (95% CI, 61.3 to 73.1) with atezolizumab-bevacizumab and 54.6% (95% CI, 45.2 to 64.0) with sorafenib. Median progression-free survival was 6.8 months (95% CI, 5.7 to 8.3) and 4.3 months (95% CI, 4.0 to 5.6) in the respective groups (hazard ratio for disease progression or death, 0.59; 95% CI, 0.47 to 0.76; P<0.001). Grade 3 or 4 adverse events occurred in 56.5% of 329 patients who received at least one dose of atezolizumab-bevacizumab and in 55.1% of 156 patients who received at least one dose of sorafenib. Grade 3 or 4 hypertension occurred in 15.2% of patients in the atezolizumab-bevacizumab group; however, other high-grade toxic effects were infrequent.
CONCLUSIONS
In patients with unresectable hepatocellular carcinoma, atezolizumab combined with bevacizumab resulted in better overall and progression-free survival outcomes than sorafenib. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT03434379.).
Identifiants
pubmed: 32402160
doi: 10.1056/NEJMoa1915745
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Programmed Cell Death 1 Receptor
0
Bevacizumab
2S9ZZM9Q9V
atezolizumab
52CMI0WC3Y
Banques de données
ClinicalTrials.gov
['NCT03434379']
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
1894-1905Investigateurs
R Asghari
(R)
V Broadbridge
(V)
L Lipton
(L)
A Zekry
(A)
J Asselah
(J)
H Castel
(H)
R Goel
(R)
P Kavan
(P)
Y Bai
(Y)
B Cao
(B)
M Chen
(M)
X Chen
(X)
Y Cheng
(Y)
W Fang
(W)
K Gu
(K)
S Gu
(S)
Y Guo
(Y)
Y He
(Y)
W Li
(W)
Z Meng
(Z)
H Pan
(H)
S Qin
(S)
Z Ren
(Z)
B Wang
(B)
W Wang
(W)
B Xing
(B)
J Ying
(J)
X Yuan
(X)
H Zhao
(H)
B Bencsikova
(B)
B Melichar
(B)
R Anty
(R)
E Assenat
(E)
J P Bronowicki
(JP)
S Cattan
(S)
F Di Fiore
(F)
M Ducreux
(M)
R Gerolami Santandrea
(R)
P Merle
(P)
M Nguimpi Tambou
(M)
Y Touchefeu
(Y)
A Tran
(A)
T Berg
(T)
A Kandulski
(A)
T Müller
(T)
J Trojan
(J)
A Vogel
(A)
H Wege
(H)
M Wörns
(M)
L Chan
(L)
T Yau
(T)
G Frassineti
(G)
D Germano
(D)
G Masi
(G)
G Scagliotti
(G)
M Scartozzi
(M)
V Zagonel
(V)
T Aramaki
(T)
A Hagihara
(A)
H Hidaka
(H)
S Hige
(S)
M Ikeda
(M)
N Kato
(N)
H Koga
(H)
M Kudo
(M)
K Ogawa
(K)
N Oza
(N)
M Tanaka
(M)
K Tsuchiya
(K)
T Yamashita
(T)
J-H Baek
(JH)
J-K Cheon
(JK)
H-J Choi
(HJ)
J-E Hwang
(JE)
T-Y Kim
(TY)
H-Y Lim
(HY)
B-Y Ryoo
(BY)
A Cencelewicz
(A)
P Hudziec
(P)
E Janczewska
(E)
P Rozanowski
(P)
M Wieczorek-Rutkowska
(M)
J Wojcik-Tomaszewska
(J)
V Breder
(V)
N Volkov
(N)
J Samol
(J)
H-C Toh
(HC)
A Cubillo Gracian
(A)
J Feli
(J)
T Macarulla Mercade
(T)
R Pazo Cid
(R)
J Sastre Valera
(J)
Y Chao
(Y)
A L Cheng
(AL)
Y-H Feng
(YH)
T-S Yang
(TS)
C-J Yen
(CJ)
J Evans
(J)
R Hubner
(R)
T Meyer
(T)
P Ross
(P)
A Baron
(A)
A Burgoyne
(A)
W Cancel
(W)
V Chiu
(V)
F Dayyani
(F)
R Finn
(R)
J Franses
(J)
P Gold
(P)
A R He
(AR)
A Kaseb
(A)
R Kim
(R)
M Kundranda
(M)
D Li
(D)
D Lin
(D)
R Salgia
(R)
J Suga
(J)
N Trikalinos
(N)
J Wu
(J)
A Zhu
(A)
Commentaires et corrections
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Informations de copyright
Copyright © 2020 Massachusetts Medical Society.