Checkpoint inhibitors in metastatic EGFR-mutated non–small cell lung cancer-a meta-analysis

Lee, Chee Khoon; Man, Johnathan; Lord, Sally; Links, Matthew; Gebski, Val; Mok, Tony; Yang, James Chih-Hsin

doi:10.1016/j.jtho.2016.10.007

Cited by 843Lung Cancer Treatments and MutationsCancer Immunotherapy and BiomarkersLung Cancer Diagnosis and Treatment

Checkpoint inhibitors in metastatic EGFR-mutated non–small cell lung cancer-a meta-analysis

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Lee, Chee Khoon, Man, Johnathan, Lord, Sally, Links, Matthew, Gebski, Val, Mok, Tony, Yang, James Chih-Hsin·2017·Journal of Thoracic Oncology

DOI 10.1016/j.jtho.2016.10.007

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Abstract

Introduction We performed a meta-analysis to assess the role of immune checkpoint inhibitors as second-line therapy in EGFR-mutant advanced NSCLC.Methods Randomized trials comparing immune checkpoint inhibitors against chemotherapy were identified. We retrieved the hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) of the intention-to-treat population and EGFR mutation-defined subgroups. We used the fixed-effects inverse variance-weighted method to pool estimates of treatment efficacy. Statistical tests were two sided.Results In the three included studies that compared immune checkpoint inhibitors (nivolumab [n = 292], pembrolizumab [n = 691], and atezolizumab [n =144]) against docetaxel (n = 776), immune checkpoint inhibitors significantly prolonged OS over that with docetaxel overall (n = 1903, HR = 0.68, 95% CI: 0.61-0.77, p < 0.0001) and in the EGFR wild-type subgroup (n = 1362, HR = 0.66, 95% CI: 0.58-0.76, p < 0.0001) but not in the EGFR-mutant subgroup (n = 186, HR = 1.05, 95% CI: 0.70-1.55, p < 0.81; treatment-mutation interaction p = 0.03).Conclusion In EGFR-mutant advanced NSCLC, immune checkpoint inhibitors do not improve OS over that with docetaxel. Mechanisms of acquired resistance to first-line tyrosine kinase inhibitor therapy should be elucidated to guide selection of second-line treatment for these patients.

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Low tumor mutational burden in EGFR exon 20 insertion cases suggests a comparable lack of benefit from single-agent PD-1/PD-L1 antibodies as in NSCLC with more common EGFR mutations.
“Overall, low TMB suggests comparable lack of benefit to single agent PD-1 / PD-L1 antibodies in EGFRex20ins NSCLC as in NSCLC harboring more common EGFR mutations.”
From Diverse EGFR Exon 20 Insertions and Co-Occurring Molecular Alterations Identified by Comprehensive Genomic Profiling of NSCLC (2018) · cites this paper as [26]

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Authors: Lee, C. K., Man, J., Lord, S., Links, M., Gebski, V., Mok, T., & Yang, J. C.-H.
Affiliations: The University of Sydney (AU)
St George Hospital (AU)
Chinese University of Hong Kong (HK)
National Taiwan University (TW)
Corresponding author: Lee, Chee Khoon
ORCID: Lee, Chee Khoon
Man, Johnathan
Links, Matthew
Gebski, Val
Mok, Tony
Yang, James Chih-Hsin
Venue: Journal of Thoracic Oncology
Publisher: Elsevier BV
Published: 2017-02
Volume: 12
Issue: 2
Pages: 403-407
ISSN: 1556-0864 (ISSN-L)
DOI: 10.1016/j.jtho.2016.10.007
OpenAlex: W2538232731
Cited by: 839
References: 15
Citations by year: 2026: 47 · 2025: 61 · 2024: 68 · 2023: 84 · 2022: 93 · 2021: 98 · 2020: 100 · 2019: 100 · 2018: 123 · 2017: 62 · 2016: 1 · 2015: 1
FWCI: 85.21
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 365 d)
Locations: Journal of Thoracic Oncology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Keywords: immune checkpoint inhibitors, EGFR-mutant non-small cell lung cancer, second-line therapy, nivolumab, pembrolizumab, atezolizumab, docetaxel, overall survival, advanced non-small cell lung cancer
MeSH terms: Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Humans, Immunotherapy, Lung Neoplasms, Mutation, Prognosis, Randomized Controlled Trials as Topic, Cell Cycle Checkpoints, ErbB Receptors

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Checkpoint inhibitors in metastatic EGFR-mutated non–small cell lung cancer-a meta-analysis

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