Exon 19 Deletion Mutations of Epidermal Growth Factor Receptor Are Associated with Prolonged Survival in Non–Small Cell Lung Cancer Patients Treated with Gefitinib or Erlotinib

Jackman, David M.; Yeap, Beow Y.; Sequist, Lecia V.; Lindeman, Neal; Holmes, Alison J.; Joshi, Victoria A.; Bell, Daphne W.; Huberman, Mark S.; Halmos, Balazs; Rabin, Michael S.; Haber, Daniel A.; Lynch, Thomas J.; Meyerson, Matthew; Johnson, Bruce E.; Jänne, Pasi A.

doi:10.1158/1078-0432.ccr-06-0462

Cited by 584Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchLung Cancer Diagnosis and Treatment

Exon 19 Deletion Mutations of Epidermal Growth Factor Receptor Are Associated with Prolonged Survival in Non–Small Cell Lung Cancer Patients Treated with Gefitinib or Erlotinib

Jackman, David M., Yeap, Beow Y., Sequist, Lecia V., Lindeman, Neal, Holmes, Alison J., Joshi, Victoria A., Bell, Daphne W., Huberman, Mark S. +7 more·2006·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-06-0462

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Abstract

PURPOSE: Somatic mutations in the epidermal growth factor receptor (EGFR) have been detected in patients with non-small cell lung cancer (NSCLC) and are associated with sensitivity to treatment with gefitinib or erlotinib. Our study explored the relationship between the two most common types of somatic EGFR mutations, exon 19 deletions and the L858R point mutation, and outcomes of patients following treatment with gefitinib or erlotinib. EXPERIMENTAL DESIGN: Tumor specimens obtained before treatment with gefitinib or erlotinib were analyzed for EGFR mutations. Patients with exon 19 deletion or L858R mutations were identified. The response rate, time to progression, and overall survival were determined for the two groups. RESULTS: We identified 36 patients with NSCLC and an EGFR mutation who were treated with gefitinib or erlotinib. Patients with an exon 19 deletion had a significantly longer overall survival compared with patients with an L858R mutation (38 versus 17 months; P = 0.04). There were also trends toward higher response rate (73% versus 50%) and improved time to progression (24 versus 10 months) for the patients with an exon 19 deletion, although these were not independently significant in a multivariate analysis. A difference in response rate for patients treated with gefitinib compared with erlotinib was also noted [18 of 23 (78%) versus 3 of 9 (33%); P = 0.04]. No obvious difference in time to progression or overall survival was noted between gefitinib- and erlotinib-treated patients. CONCLUSIONS: Patients with NSCLC and EGFR exon 19 deletions have a longer survival following treatment with gefitinib or erlotinib compared with those with the L858R mutation. Pooling of greater numbers of patients and completion of prospective trials are needed to further define the predictive and prognostic roles of different EGFR mutations with respect to treatment with gefitinib, erlotinib, and other EGFR inhibitors.

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Multiple studies have affirmed the favorable prognostic impact of exon 19 EGFR deletions compared with exon 21 L858R substitution.
“Multiple studies have affirmed the favorable prognostic impact of exon 19 EGFR deletions compared with exon 21 L858R amino acid substitution, although the molecular basis for this association has not been conclusively determined44, 45.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [44]

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Authors: Jackman, D. M., Yeap, B. Y., Sequist, L. V., Lindeman, N., Holmes, A. J., Joshi, V. A., Bell, D. W., Huberman, M. S., Halmos, B., Rabin, M. S., Haber, D. A., Lynch, T. J., Meyerson, M., Johnson, B. E., & Jänne, P. A.
Affiliations: 1Lowe Center of Thoracic Oncology, Department of Medical Oncology and
3Medicine and
Massachusetts General Hospital (US)
8Pathology and
Harvard University (US)
Beth Israel Deaconess Medical Center (US)
12Ireland Cancer Center, University Hospitals of Cleveland, Case School of Medicine, Cleveland, Ohio
Brigham and Women's Hospital (US)
ORCID: Yeap, Beow Y.
Sequist, Lecia V.
Lindeman, Neal
Bell, Daphne W.
Rabin, Michael S.
Haber, Daniel A.
Lynch, Thomas J.
Meyerson, Matthew
Johnson, Bruce E.
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2006-07-01
Volume: 12
Issue: 13
Pages: 3908-3914
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-06-0462
OpenAlex: W2168841302
Cited by: 584
References: 6
Citations by year: 2026: 4 · 2025: 13 · 2024: 13 · 2023: 22 · 2022: 22 · 2021: 26 · 2020: 20 · 2019: 22 · 2018: 32 · 2017: 33 · 2016: 32 · 2015: 38 · 2014: 30 · 2013: 30 · 2012: 33
FWCI: 38.90
Type: journal article
Language: en
Open access: closed
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (R01CA114465, P20CA090578, P20 CA 90578-02, 1K12CA87723-01)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Keywords: EGFR exon 19 deletion, L858R mutation, non-small cell lung cancer, gefitinib, erlotinib, EGFR inhibitors, overall survival, time to progression, treatment response, predictive biomarkers, prognostic factors
MeSH terms: Erlotinib Hydrochloride, Gefitinib, Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, DNA Mutational Analysis, DNA, Neoplasm, Exons, Female, Follow-Up Studies, Genotype, Humans, Lung Neoplasms, Male, Middle Aged, Neoplasm Staging, Quinazolines, Retrospective Studies, Survival Rate, Treatment Outcome, Point Mutation, Sequence Deletion, Disease Progression, ErbB Receptors

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Exon 19 Deletion Mutations of Epidermal Growth Factor Receptor Are Associated with Prolonged Survival in Non–Small Cell Lung Cancer Patients Treated with Gefitinib or Erlotinib

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