Clinical and molecular characteristics of non-small-cell lung cancer (NSCLC) harboring EGFR mutation: results of the nationwide French Cooperative Thoracic Intergroup (IFCT) program

C Leduc; J P Merlio; B Besse; H Blons; D Debieuvre; P P Bringuier; I Monnet; I Rouquette; S Fraboulet-Moreau; A Lemoine; D Pouessel; J Mosser; F Vaylet; A Langlais; P Missy; F Morin; D Moro-Sibilot; J Cadranel; F Barlesi; M Beau-Faller; French Cooperative Thoracic Intergroup (IFCT)

doi:10.1093/annonc/mdx404

Clinical and molecular characteristics of non-small-cell lung cancer (NSCLC) harboring EGFR mutation: results of the nationwide French Cooperative Thoracic Intergroup (IFCT) program

Ann Oncol. 2017 Nov 1;28(11):2715-2724. doi: 10.1093/annonc/mdx404.

Authors

C Leduc¹, J P Merlio², B Besse³, H Blons⁴, D Debieuvre⁵, P P Bringuier⁶, I Monnet⁷, I Rouquette⁸, S Fraboulet-Moreau⁹, A Lemoine¹⁰, D Pouessel¹¹, J Mosser¹², F Vaylet¹³, A Langlais¹⁴, P Missy¹⁵, F Morin¹⁵, D Moro-Sibilot¹⁶, J Cadranel¹⁷, F Barlesi¹⁸, M Beau-Faller¹⁹; French Cooperative Thoracic Intergroup (IFCT)

Affiliations

¹ Department of Chest, Centre Hospitalier Universitaire de Strasbourg, Nouvel Hôpital Civil, Strasbourg.
² Department of Biology and Pathology, Centre Hospitalier Universitaire de Bordeaux, Pessac;; Histology and Molecular Pathology of Tumors, Université de Bordeaux, Bordeaux.
³ Medicine Department, Gustave Roussy Cancer Campus, Villejuif.
⁴ INSERM UMR-S1147, Université Sorbonne Paris Cité, Paris;; Department of Biochemistry, Pharmacogenetics and Molecular Oncology, Hôpital Européen Georges Pompidou (HEGP), Assistance Publique - Hôpitaux de Paris, Paris.
⁵ Department of Chest, Hôpital Emile Muller - GHRMSA, Mulhouse.
⁶ Department of Biology and Pathology, Hospices Civils de Lyon, Lyon;; Université Claude Bernard Lyon 1, Lyon.
⁷ Pneumology Department, Centre Hospitalier Intercommunal de Créteil, Créteil.
⁸ Pathology Department, Centre Hospitalier Universitaire de Toulouse Institut Universitaire du Cancer de Toulouse, Oncopôle, Toulouse.
⁹ Department of Chest, Hôpital Foch, Suresnes.
¹⁰ Biochemistry and Oncogenetic Department, Oncomolpath, Assistance Publique - Hôpitaux de Paris, Paris;; Groupe Hospitalier des Hôpitaux Universitaires Paris-Sud, Université Paris 11, Villejuif.
¹¹ Medical Oncology Department, Hôpital Saint Louis, Assistance Publique - Hôpitaux de Paris, Paris.
¹² Department of Molecular Genetics and Genomics - Medical Genomics, Centre Hospitalier Universitaire de Rennes, Rennes.
¹³ Department of Chest, Hôpital d'Instruction des Armées Percy, Clamart.
¹⁴ Department of Biostatistics, Francophone de Cancérologie Thoracique, Paris.
¹⁵ Clinical Research Unit, Intergroupe Francophone de Cancérologie Thoracique, Paris.
¹⁶ Thoracic Oncology Unit, Centre Hospitalier Universitaire Grenoble-Alpes, Clinique de Pneumologie, Grenoble.
¹⁷ Department of Chest, Assistance Publique - Hôpitaux de Paris, Hôpital Tenon, Paris;; Sorbonne Université, UPMC Univ Paris 06, GRC n-04, Theranoscan, Paris.
¹⁸ Assistance Publique - Hôpitaux de Marseille, Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Centre d'Investigation Clinique, Marseille.
¹⁹ Laboratory of Biochemistry and Molecular Biology, Centre Hospitalier Universitaire de Strasbourg, Hôpital de Hautepierre, Strasbourg;; EA3430 "Progression Tumorale et Microenvironnement, Approches Translationnelles et Épidémiologie," Strasbourg, France. Electronic address: michele.faller@chru-strasbourg.fr.

PMID: 28945865
DOI: 10.1093/annonc/mdx404

Abstract

Background: EGFR mutations cause inconsistent response to EGFR tyrosine-kinase inhibitors (TKI). To better understand these features, we reviewed all cases of EGFR-mutated non-small-cell lung cancer collected in the Biomarkers France database.

Patients and methods: Of 17 664 patients, 1837 (11%) with EGFR-mutated non-small-cell lung cancer were retrospectively analyzed for clinical and molecular characteristics. Results were correlated with survival and treatment response for the 848 stage IV patients.

Results: EGFR exon 18, 19, 20 and 21 mutations were found in 102 (5.5%), 931 (51%), 102 (5.5%) and 702 (38%) patients, respectively. Over 50% of exon 18 and 20 mutated patients were smokers. The median follow-up was 51.7 months. EGFR mutation type was prognostic of overall survival (OS) versus wild-type {exon 19: hazard ratio (HR)=0.51 [95% confidence interval (CI): 0.41-0.64], P < 0.0001; exon 21: HR = 0.76 (95% CI: 0.61-0.95), P = 0.002; exon 20: HR = 1.56 (95% CI: 1.02-2.38), P = 0.004}. EGFR mutation type was prognostic of progression-free survival versus wild-type [exon 19: HR = 0.62 (95% CI: 0.49-0.78), P < 0.0001; exon 20: HR = 1.46 (95% CI: 0.96-2.21), P = 0.07]. First-line treatment choice did not influence OS in multivariate analysis. First-line TKI predicted improved progression-free survival versus chemotherapy [HR = 0.67 (95% CI: 0.53-0.85), P = 0.001]. OS was longer for del19 versus L858R, which was associated with better OS compared with other exon 21 mutations, including L861Q. TKI improved survival in patients with exon 18 mutations, while chemotherapy was more beneficial for exon 20-mutated patients.

Conclusion: EGFR mutation type can inform the most appropriate treatment. Therapeutic schedule had no impact on OS in our study, although TKI should be prescribed in first-line considering the risk of missing the opportunity to use this treatment.

Keywords: epidemiology; epidermal growth factor receptor gene (EGFR) mutations; non-small-cell lung cancer (NSCLC); tyrosine-kinase inhibitors (TKI).

MeSH terms

Biomarkers, Tumor / genetics*
Carcinoma, Non-Small-Cell Lung / drug therapy
Carcinoma, Non-Small-Cell Lung / genetics
Carcinoma, Non-Small-Cell Lung / pathology*
ErbB Receptors / antagonists & inhibitors
ErbB Receptors / genetics*
Follow-Up Studies
France
Humans
Lung Neoplasms / drug therapy
Lung Neoplasms / genetics
Lung Neoplasms / pathology*
Mutation*
Prognosis
Protein Kinase Inhibitors / therapeutic use*
Retrospective Studies
Survival Rate

Substances

Biomarkers, Tumor
Protein Kinase Inhibitors
EGFR protein, human
ErbB Receptors