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Checkpoint inhibitors in metastatic EGFR-mutated non–small cell lung cancer-a meta-analysis
Open accessAbstract
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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“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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Metadata
- 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
- Venue
- Journal of Thoracic Oncology
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 12
- Issue
- 2
- Pages
- 403-407
- ISSN
- 1556-0864 (ISSN-L)
- 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
- FWCI
- 85.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- 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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