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Atezolizumab plus bevacizumab and chemotherapy in metastatic nonsquamous NSCLC: the randomized double-blind phase 3 IMpower151 trial
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Atezolizumab plus bevacizumab and chemotherapy in metastatic nonsquamous NSCLC: the randomized double-blind phase 3 IMpower151 trial
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Journal Article
Atezolizumab plus bevacizumab and chemotherapy in metastatic nonsquamous NSCLC: the randomized double-blind phase 3 IMpower151 trial
2025
Overview
After the global approval of atezolizumab plus bevacizumab and chemotherapy as first-line metastatic nonsquamous non-small-cell lung cancer (nsqNSCLC) treatment, the IMpower151 (
NCT04194203
) trial was conducted in China to address regional differences. Chemotherapy-naive patients with metastatic nsqNSCLC (
N
= 305) were randomized 1:1 to receive either atezolizumab, bevacizumab, carboplatin and paclitaxel or pemetrexed (ABCPem/Pac;
n
= 152) or placebo plus bevacizumab, carboplatin and pemetrexed or paclitaxel (BCPem/Pac;
n
= 153). The primary endpoint was investigator-assessed progression-free survival (INV-PFS); secondary endpoints included subgroup analyses of INV-PFS, independent review facility-assessed PFS, overall survival, and investigator-assessed objective response rate and duration of response per RECIST v.1.1. Most patients (97%) received pemetrexed, and 53% had
EGFR
+
tumors. Median INV-PFS for ABCPem/Pac versus BCPem/Pac was 9.5 versus 7.1 months (stratified hazard ratio: 0.84; 95% confidence interval: 0.65, 1.09;
P
= 0.184). INV-PFS across subgroups and independent review facility-assessed PFS were consistent with INV-PFS in the intention-to-treat population. Median overall survival was 20.7 versus 18.7 months in the ABCPem/Pac versus BCPem/Pac arms, respectively (stratified hazard ratio: 0.93; 95% confidence interval: 0.67, 1.28). Confirmed objective response rate with ABCPem/Pac versus BCPem/Pac was 48% versus 50%, respectively; median duration of response was 11.3 versus 8.3 months. Adverse events of special interest for atezolizumab were observed in 68% (grades 3 and 4: 11%) and 71% (grades 3 and 4: 7%) of patients receiving ABCPem/Pac and BCPem/Pac, respectively. The most common adverse events of special interest for atezolizumab in the ABCPem/Pac and BCPem/Pac arms were hepatitis (driven by laboratory abnormalities; mostly low grade), hypothyroidism and rash. Overall, IMpower151 did not meet its primary endpoint (INV-PFS) in metastatic nsqNSCLC. ABCPem/Pac was generally well tolerated, with no new safety signals. Trial registration number: ClinicalTrials.gov,
NCT02366143
In the IMpower151 trial, the drug combination previously shown to be effective in the IMpower150 trial was not significantly effective in a Chinese population.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Adult
/ Aged
/ Antibodies, Monoclonal, Humanized - administration & dosage
/ Antibodies, Monoclonal, Humanized - adverse effects
/ Antibodies, Monoclonal, Humanized - therapeutic use
/ Antineoplastic Combined Chemotherapy Protocols - adverse effects
/ Antineoplastic Combined Chemotherapy Protocols - therapeutic use
/ Bevacizumab - administration & dosage
/ Bevacizumab - adverse effects
/ Bevacizumab - therapeutic use
/ Biomedical and Life Sciences
/ Carboplatin - administration & dosage
/ Carcinoma, Non-Small-Cell Lung - drug therapy
/ Carcinoma, Non-Small-Cell Lung - genetics
/ Carcinoma, Non-Small-Cell Lung - mortality
/ Carcinoma, Non-Small-Cell Lung - pathology
/ Female
/ Females
/ Humans
/ Kinases
/ Lung Neoplasms - drug therapy
/ Male
/ Mutation
/ Non-small cell lung carcinoma
/ Paclitaxel - administration & dosage
/ Patients
/ Pemetrexed - administration & dosage
/ Survival
/ Tumors
