Clinical Outcomes in Non-Small Cell Lung Cancers Harboring Different Exon 19 Deletions in EGFR
Menée sur 308 patients atteints d'un cancer du poumon non à petites cellules, cette étude évalue l'association entre divers types de délétions de l'exon 19 du gène EGFR et la réponse à un traitement par inhibiteur de l'activité tyrosine kinase d'EGFR
Purpose Several deletions in exon 19 of epidermal growth factor receptor gene (EGFR) have been reported in non-small cell lung cancer (NSCLC). It is unknown if deletions occurring at different amino acid positions or of different sizes are associated with different clinical outcome to EGFR tyrosine kinase inhibitors (TKIs). Experimental Design This study enrolled NSCLC patients with deletions in EGFR exon 19. Patients who had received EGFR TKIs for advanced NSCLC were further evaluated for response rate (RR), progression-free survival (PFS), and overall survival (OS). Results In 308 patients with deletions in EGFR exon 19, 298 had deletions encompassing the entire amino acid string from L747 through E749 (LRE deletions). EGFR TKIs were used in 204 patients with advanced NSCLC. Patients with non-LRE deletions had the least RR, compared to those with deletions from E746 or L747 (42.9%, 68.2%, and 79.6%, respectively; P = 0.022). Patients with non-LRE deletions had relatively short median PFS, though not significantly different from those with deletions from E746 or L747 (5.9, 9.8, and 10.5 months, respectively; P = 0.665). The OS were not different among patients with deletions occurring at different amino acid positions (P = 0.776). Deletions in exon 19 of different sizes were not associated with different RR, PFS, or OS. Conclusions Non-LRE deletions in exon 19 were associated with worse response to EGFR TKIs, compared to LRE deletions. Therefore, the expected clinical outcome under EGFR TKIs depends on not only the existence but also the types of deletions in exon 19.
Clinical Cancer Research , résumé, 2012