Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer

Rosell, Rafael; Moran, Teresa; Queralt, Cristina; Porta, Rut; Cardenal, Felipe; Camps, Carlos; Majem, Margarita; Lopez-Vivanco, Guillermo; Isla, Dolores; Provencio, Mariano; Insa, Amelia; Massuti, Bartomeu; Gonzalez-Larriba, Jose Luis; Paz-Ares, Luis; Bover, Isabel; Garcia-Campelo, Rosario; Moreno, Miguel Angel; Catot, Silvia; Rolfo, Christian; Reguart, Noemi; Palmero, Ramon; Sánchez, José Miguel; Bastus, Roman; Mayo, Clara; Bertran-Alamillo, Jordi; Molina, Miguel Angel; Sanchez, Jose Javier; Taron, Miquel

doi:10.1056/nejmoa0904554

Cited by 2,373Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchLung Cancer Diagnosis and Treatment

Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer

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Rosell, Rafael, Moran, Teresa, Queralt, Cristina, Porta, Rut, Cardenal, Felipe, Camps, Carlos, Majem, Margarita, Lopez-Vivanco, Guillermo +20 more·2009·New England Journal of Medicine

DOI 10.1056/nejmoa0904554

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Abstract

BACKGROUND: Activating mutations in the epidermal growth factor receptor gene (EGFR) confer hypersensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in patients with advanced non-small-cell lung cancer. We evaluated the feasibility of large-scale screening for EGFR mutations in such patients and analyzed the association between the mutations and the outcome of erlotinib treatment. METHODS: From April 2005 through November 2008, lung cancers from 2105 patients in 129 institutions in Spain were screened for EGFR mutations. The analysis was performed in a central laboratory. Patients with tumors carrying EGFR mutations were eligible for erlotinib treatment. RESULTS: EGFR mutations were found in 350 of 2105 patients (16.6%). Mutations were more frequent in women (69.7%), in patients who had never smoked (66.6%), and in those with adenocarcinomas (80.9%) (P<0.001 for all comparisons). The mutations were deletions in exon 19 (62.2%) and L858R (37.8%). Median progression-free survival and overall survival for 217 patients who received erlotinib were 14 months and 27 months, respectively. The adjusted hazard ratios for the duration of progression-free survival were 2.94 for men (P<0.001); 1.92 for the presence of the L858R mutation, as compared with a deletion in exon 19 (P=0.02); and 1.68 for the presence of the L858R mutation in paired serum DNA, as compared with the absence of the mutation (P=0.02). The most common adverse events were mild rashes and diarrhea; grade 3 cutaneous toxic effects were recorded in 16 patients (7.4%) and grade 3 diarrhea in 8 patients (3.7%). CONCLUSIONS: Large-scale screening of patients with lung cancer for EGFR mutations is feasible and can have a role in decisions about treatment.

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Most patients with exon 19 deletions or L858R have radiographic responses to gefitinib, erlotinib, and afatinib.
“Most patients whose tumors harbor exon 19 deletions or L858R EGFR activating mutations have radiographic responses to monotherapy with the reversible adenosine triphosphate (ATP)-competitive EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib 17–23 and the irreversible EGFR TKI afatinib 24.”
From Structural, Biochemical, and Clinical Characterization of Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations in Lung Cancer (2013) · cites this paper as [19]
Since no survival gain was demonstrated in phase III trials, the use of EGFR TKIs in EGFR-mutated patients in first- or second-line should not influence eventual survival outcome, as demonstrated in the phase II trial of the Spanish Lung Cancer Group.
“Since no survival gain was demonstrated in the phase III trials conducted so far, the use of EGFR TKIs in EGFR-mutated patients in first- or second-line should not influence the eventual survival outcome, as demonstrated in the phase II trial of the Spanish Lung Cancer Group [40].”
From A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives (2015) · cites this paper as [40]

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Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to Gefitinib
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Authors: Rosell, R., Moran, T., Queralt, C., Porta, R., Cardenal, F., Camps, C., Majem, M., Lopez-Vivanco, G., Isla, D., Provencio, M., Insa, A., Massuti, B., Gonzalez-Larriba, J. L., Paz-Ares, L., Bover, I., Garcia-Campelo, R., Moreno, M. A., Catot, S., Rolfo, C., Reguart, N., Palmero, R., Sánchez, J. M., Bastus, R., Mayo, C., Bertran-Alamillo, J., Molina, M. A., Sanchez, J. J., & Taron, M.
Affiliations: Universitat Autònoma de Barcelona (ES)
Institut Català d'Oncologia (ES)
Hospital General Universitario De Valencia (ES)
Hospital de Sant Pau (ES)
Hospital Clínico Universitario Lozano Blesa (ES)
Hospital Clínico Universitario de Valencia (ES)
Hospital Universitario Virgen del Rocío (ES)
Hospital Son Llatzer (ES)
Clinica Rotger (ES)
Hospital Universitario 12 De Octubre (ES)
USP Institut Universitari Dexeus (ES)
ORCID: Rosell, Rafael
Queralt, Cristina
Camps, Carlos
Majem, Margarita
Isla, Dolores
Provencio, Mariano
Insa, Amelia
Paz-Ares, Luis
Rolfo, Christian
Sánchez, José Miguel
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2009-09-03
Volume: 361
Issue: 10
Pages: 958-967
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa0904554
OpenAlex: W2095618958
Cited by: 2,373
References: 8
Citations by year: 2026: 35 · 2025: 68 · 2024: 69 · 2023: 90 · 2022: 109 · 2021: 110 · 2020: 100 · 2019: 111 · 2018: 116 · 2017: 160 · 2016: 143 · 2015: 190 · 2014: 202 · 2013: 229 · 2012: 198
FWCI: 179.89
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: other-oa
Locations: New England Journal of Medicine (publishedVersion, other-oa)
PubMed (publishedVersion)
Hispana (publishedVersion)
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 mutation, non-small cell lung cancer, erlotinib, gefitinib, tyrosine kinase inhibitors, exon 19 deletion, L858R mutation, progression-free survival, overall survival, serum DNA, skin toxicity, adenocarcinoma, smoking status
MeSH terms: Erlotinib Hydrochloride, Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Diarrhea, Exanthema, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Prospective Studies, Quinazolines, Multivariate Analysis, Survival Analysis, Sex Distribution, Protein Kinase Inhibitors, Kaplan-Meier Estimate, Young Adult, ErbB Receptors

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