Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Treatment Response in Advanced Non-Small Cell Lung Cancer with G719X/L861Q/S768I Mutations

Abstract

ABSTRACT Aim: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are very effective for lung cancers with classical sensitive EGFR mutations; however, their role in tumors with uncommon mutations, such as G719X, L861Q and S768I, is still not clear. Previous studies are limited by their small sample size. Taiwan Lung Cancer Society, in conjunction with Taiwan Lung Cancer Clinical Trial Consortium, initiated a study to evaluate the clinical effectiveness of EGFR-TKI in patients with advanced non-small cell lung carcinoma (NSCLC) bearing EGFR G719X, L861Q and/or S768I mutations. Methods: Patients were eligible if they had stage IIIB or IV NSCLC bearing G719X, L861Q or S768I mutations, had been treated by gefitinib or erlotinib, and did not receive other anti-tumor therapy during EGFR-TKI treatment. Patients with tumors that had concomittant classical sensitive (exon 19 deletions and L858R mutation) or resistant (T790M and exon 20 insertions) mutations were excluded. Results: Totally 226 cases were screened from 18 institutes throughout Taiwan. One hundred and sixty-one cases were eligible and all were adenocarcinomas. Among them, 56.5% were female, 68.8% were never smokers, 95.7% were stage IV, 76.4% were PS 0-1, and 78.9% were treatment-naive. EGFR mutation status were G719X of 78 cases, L861Q of 58, S768I of 7, G719X + L861Q of 8, and G719X + S768I of 10. One hundred and twenty-seven patients were treated by gefitinib and 34 by erlotinib. Four hundred and eighty-three patients who had classical sensitive EGFR mutations and were treated by EGFR-TKI were served as the control. EGFR-TKI treatment outcomes are summarized in the Table. Patients with G719X/L861Q/S768I mutations had inferior response rate and shorter progression free survival than patients with exon 19 deletions or L858R mutations (both P ORR DCR PFS G719X/L861Q/S768I (n = 161) 40.5% 75.8% 7.7m L858R mutations (n = 253) 67.6% 95.7% 10.4m exon 19 deletions (n = 223) 64.5% 94.6% 14.1m Conclusions: Patients with advanced lung adenocarcinomas of EGFR G719X/L861Q/S768I mutations had suboptimal treatment outcome to EGFR-TKI. Prospective randomized trials are warranted to decide the most appropriate therapy for patients with these uncommon mutations. Disclosure: C. Chiu: I have received honorarium from AstraZeneca, Boehringer Ingelheim and Roche. All other authors have declared no conflicts of interest.