Prognostic Value of Exon 19 Versus 21 EGFR Mutations Varies According to Disease Stage in Surgically Resected Non-small Cell Lung Cancer Adenocarcinoma
(2018) Annals of Surgical Oncology — Vol. 25, n° 4, p. 1069-1078 (2018)
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- Background. The prognostic value of exon 19 and 21 EGFR mutations in stage IV non-small cell lung cancer (NSCLC) is well established. Objective. We aimed to evaluate the prognostic value of the mutations in surgically resected NSCLC. Methods. We retrospectively reviewed data from 1798 surgically resected NSCLC adenocarcinomas between 2007 and 2017 in three departments of thoracic surgery (Nancy/ Strasbourg, France, and Torino, Italy) for whom mutational status was known. Overall survival (OS) was evaluated using log-rank and Cox proportional hazard models. Results. EGFR exon 19 deletion was observed in 108 patients (55.1%) and exon 21 L858R mutations were observed in 88 patients (44.9%). In stage I, the median OS was not significantly different between exons 19 and 21 (p = 0.54), while, in stage II, the median OS reached 65 months [95% confidence interval (CI) 41.67-88.33] for exon 19 mutations and decreased to 48 months for exon 21 mutations (95% CI 44.21-51.79; p = 0.027). In multivariate analysis, exon 19 deletion remained a favorable prognostic factor [hazard ratio (HR) 0.314, 95% CI 0.098-0.997; p = 0.05]. In stage III, the median OS reached 66 months (95% CI 44.67-87.32) for exon 19 mutations and decreased to 32 months for exon 21 mutations (95% CI 29.86-34.14; p = 0.03). In multivariate analysis, exon 19 deletion remained a significantly favorable prognostic factor (HR 0.165, 95% CI 0.027-0.999; p = 0.05). Conclusion. The prognostic value of EGFR exon 19 and 21 mutations appears to be different according to disease stage in surgically resected NSCLC. Lung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for nearly 85% of lung cancer cases. The past decades have seen a dramatic increase in the understanding of molecular alterations of NSCLC, particularly with the discovery of oncogenic drivers, allowing clinicians to define prognosis more accurately and adapt therapies in metastatic NSCLC, thus offering new hope to patients. 1 Mutations in the gene encoding the epidermal growth factor receptor (EGFR) have likely been the most extensively studied. 2 EGFR mutations occur mainly in NSCLC adenocarcinomas, females, non-smokers, and Asian patients. Overall, 80% of the mutations are represented by exon 19 deletions and exon 21 L858R mutations. Electronic supplementary material The online version of this article (https://doi.org/10.1245/s10434-018-6347-3) contains supplementary material, which is available to authorized users.
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Renaud, S., Seitlinger, J., Guerrera, F., Reeb, J., Beau-Faller, M., Voegeli, A.-C., Siat, J., Clément-Duchêne, C., Tiotiu-Cepuc, I., Santelmo, N., Costardi, L., Ruffini, E., Falcoz, P.-E., Vignaud, J.-M., & Massard, G. (2018). Prognostic Value of Exon 19 Versus 21 EGFR Mutations Varies According to Disease Stage in Surgically Resected Non-small Cell Lung Cancer Adenocarcinoma. Annals of Surgical Oncology, 25(4), 1069-1078. https://doi.org/10.1245/s10434-018-6347-3 (Original work published 2018)