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Cited by 581Lung Cancer Treatments and MutationsCancer Immunotherapy and BiomarkersLung Cancer Diagnosis and Treatment

The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.

A Phase II Study of Pembrolizumab in EGFR-Mutant, PD-L1+, Tyrosine Kinase Inhibitor Naïve Patients With Advanced NSCLC

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Lisberg, A., Cummings, A., Goldman, J.W., Bornazyan, K., Reese, N., Wang, T., Coluzzi, P., Ledezma, B., Mendenhall, M., Hunt, J., Wolf, B., Jones, B., Madrigal, J., Horton, J., Spiegel, M., Carroll, J., Gukasyan, J., Williams, T., Sauer, L., Wells, C., Hardy, A., Linares, P., Lim, C., Ma, L., Adame, C., Garon, Edward B.·2018·Journal of Thoracic Oncology
DOI 10.1016/j.jtho.2018.03.035PMC PMC6063769
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Abstract

Background Despite the significant antitumor activity of pembrolizumab in NSCLC, clinical benefit has been less frequently observed in patients whose tumors harbor EGFR mutations compared to EGFR wild-type patients. Our single-center experience on the KEYNOTE-001 trial suggested that pembrolizumab-treated EGFR-mutant patients, who were tyrosine kinase inhibitor (TKI) naïve, had superior clinical outcomes to those previously treated with a TKI. As TKI naïve EGFR-mutants have generally been excluded from pembrolizumab studies, data to guide treatment decisions in this patient population is lacking, particularly in patients with programmed death ligand 1 (PD-L1) expression ≥50%.Methods We conducted a phase II trial (NCT02879994) of pembrolizumab in TKI naive patients with EGFR mutation-positive, advanced NSCLC and PD-L1-positive (≥1%, 22C3 antibody) tumors. Pembrolizumab was administered 200 mg every 3 weeks. The primary endpoint was objective response rate. Secondary endpoints included safety of pembrolizumab, additional pembrolizumab efficacy endpoints, and efficacy and safety of an EGFR TKI after pembrolizumab.Results Enrollment was ceased due to lack of efficacy after 11 of 25 planned patients were treated. Eighty-two percent of trial patients were treatment naïve, 64% had sensitizing EGFR mutations, and 73% had PD-L1 expression ≥50%. Only 1 patient had an objective response (9%), but repeat analysis of this patient's tumor definitively showed the original report of an EGFR mutation to be erroneous. Observed treatment-related adverse events were similar to prior experience with pembrolizumab, but two deaths within 6 months of enrollment, including one attributed to pneumonitis, were of concern.Conclusions Pembrolizumab's lack of efficacy in TKI naïve, PD-L1+, EGFR-mutant patients with advanced NSCLC, including those with PD-L1 expression ≥50%, suggests that it is not an appropriate therapeutic choice in this setting.

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Research works printed but not linked: 3

  1. Hellmann, 2015, MINI03.05 Efficacy of Pembrolizumab in Key Subgroups of Patients with Advanced NSCLC, J Thorac Oncol, 10, S261
  2. Hu-Lieskovan S, et al. High Intratumoral T Cell Infiltration Correlated with Mutational Load and Response to Pembrolizumab in Non–Small Cell Lung Cancer. Paper presented at the 16th World Conference on Lung Cancer. Denver, Colorado: 2015.
  3. Garon, 2015, Prior TKI therapy in NSCLC EGFR mutant patients associates with lack of response to anti-PD-1 treatment, J Thorac Oncol, 10, S269

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Metadata

Authors
Lisberg, A., Cummings, A., Goldman, J. W., Bornazyan, K., Reese, N., Wang, T., Coluzzi, P., Ledezma, B., Mendenhall, M., Hunt, J., Wolf, B., Jones, B., Madrigal, J., Horton, J., Spiegel, M., Carroll, J., Gukasyan, J., Williams, T., Sauer, L., Wells, C., Hardy, A., Linares, P., Lim, C., Ma, L., Adame, C., & Garon, E. B.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Garon, Edward B.
ORCID
Venue
Journal of Thoracic Oncology
Publisher
Elsevier BV
Published
2018-08
Volume
13
Issue
8
Pages
1138-1145
ISSN
1556-0864 (ISSN-L)
DOI
10.1016/j.jtho.2018.03.035
PMC
PMC6063769
OpenAlex
W2889653218
Cited by
580
References
27
Citations by year
2026: 29 · 2025: 63 · 2024: 78 · 2023: 74 · 2022: 81 · 2021: 87 · 2020: 78 · 2019: 71 · 2018: 19
FWCI
48.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Thoracic Oncology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
National Institutes of Health
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
pembrolizumab, EGFR-mutant non-small cell lung cancer, PD-L1 expression, immune checkpoint inhibitors, objective response rate, treatment-related adverse events, pneumonitis, EGFR tyrosine kinase inhibitors
MeSH terms
Adult, Aged, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Protein Kinase Inhibitors, B7-H1 Antigen, Antibodies, Monoclonal, Humanized, ErbB Receptors

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