Clinical and molecular characteristics of non-small-cell lung cancer (NSCLC) harboring EGFR mutation: results of the nationwide French Cooperative Thoracic Intergroup (IFCT) program
Open accessAbstract
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.
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Proximal exon 18 substitutions show the highest sensitivity to anti-EGFR blockage.
“with proximal exon 18 substitutions showing the highest sensitivity to anti-EGFR blockage [32,33].”
Patients harboring exon 18 mutations benefit from EGFR TKI as first-line treatment compared with chemotherapy, with median PFS 14.6 months vs 5.8 months.
“Patients harboring exon 18 mutations benefit from EGFR TKI as first-line treatment, as opposed to chemotherapy (median PFS 14.6 months vs. 5.8 months)”
Exon 18 mutations have similar sensitivity to chemotherapy as EGFR wild type and other EGFR mutants.
“with similar sensitivity to chemotherapy as observed in both EGFR wild type and other EGFR mutants [32].”
Uncommon exon 21 mutations are collectively associated with lower sensitivity to EGFR TKIs compared with classic L858R, with shorter median PFS (4.5 vs 10.4 months, p=0.003) and OS (12.2 vs 16.9 months, p=0.04).
“These uncommon exon 21 mutations are collectively associated with lower sensitivity to the EGFR TKIs, compared with the classic L858R mutation, with a shorter median PFS (4.5 months vs. 10.4 months, p = 0.003) and overall survival (OS, 12.2 months vs. 16.9 months, p = 0.04) [32].”
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“0 5 10 15 20 25 PFS (month) 0 5 10 15 20 25 PFS (months) 19 20 E xon 21 22 E xon 20 21 E762G (n=1) R831C (n=1) R831H (n=1) R832H (n=1) V834M (n=1) D837E (n=1) A839S (n=1) P848L (n=7) V851I (n=1) I853N (n=1) G857E (n=1) L858M (n=1) L858Q (n=1) L858R (n=441) L861Q (n=28) G863V (n=1) E865D (n=1) A871E (n=1) A767T (n=1) A…”
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- Authors
- Leduc, C., Merlio, J. P., Besse, B., Blons, H., Debieuvre, D., Bringuier, P. P., Monnet, I., Rouquette, I., Fraboulet-Moreau, S., Lemoine, A., Pouessel, D., Mosser, J., Vaylet, F., Langlais, A., Missy, P., Morin, F., Moro-Sibilot, D., Cadranel, J., Barlesi, F., & Beau-Faller, M.
- Affiliations
- Hôpitaux Universitaires de Strasbourg (FR)
- Université de Bordeaux (FR)
- Institut Gustave Roussy (FR)
- Inserm (FR)
- Groupe Hospitalier de la Région de Mulhouse et Sud Alsace (FR)
- Lyon 1 Université (FR)
- Hôpital Intercommunal de Créteil (FR)
- Centre Hospitalier Universitaire de Toulouse (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Centre Hospitalier Universitaire de Rennes (FR)
- Hôpital d'instruction des Armées Percy (FR)
- Intergroupe Francophone de Cancérologie Thoracique (FR)
- Sorbonne Université (FR)
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 28
- Issue
- 11
- Pages
- 2715-2724
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2761632169
- Cited by
- 96
- References
- 25
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 10 · 2023: 11 · 2022: 11 · 2021: 22 · 2020: 12 · 2019: 12 · 2018: 6 · 2017: 1
- FWCI
- 7.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- EGFR-mutant non-small cell lung cancer, EGFR tyrosine kinase inhibitors, EGFR exon 19 deletion, L858R mutation, exon 20 insertion, prognostic factors, overall survival, progression-free survival, first-line therapy, smoking, stage IV lung cancer, treatment response
- MeSH terms
- Carcinoma, Non-Small-Cell Lung, Follow-Up Studies, France, Humans, Lung Neoplasms, Mutation, Prognosis, Retrospective Studies, Biomarkers, Tumor, Survival Rate, Protein Kinase Inhibitors, ErbB Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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