Clinical outcomes and secondary epidermal growth factor receptor (EGFR) T790M mutation among first‐line gefitinib, erlotinib and afatinib‐treated non‐small cell lung cancer patients with activating EGFR mutations

• Published in: International journal of cancer Vol. 144; no. 11; pp. 2887 - 2896
• Main Authors: Lin, Yen‐Ting, Chen, Jin‐Shing, Liao, Wei‐Yu, Ho, Chao‐Chi, Hsu, Chia‐Lin, Yang, Ching‐Yao, Chen, Kuan‐Yu, Lee, Jih‐Hsiang, Lin, Zhong‐Zhe, Shih, Jin‐Yuan, Yang, James Chih‐Hsin, Yu, Chong‐Jen
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.06.2019; Wiley Subscription Services, Inc
• Subjects: Cancer; Clinical outcomes; Clonal deletion; EGFR mutation; EGFR TKI; Epidermal growth factor; Epidermal growth factor receptors; Gefitinib; Gene deletion; Health risk assessment; Inhibitor drugs; Liver; Lung cancer; Medical research; Metastases; Metastasis; Multivariate analysis; Mutation; Non-small cell lung carcinoma; NSCLC; Patients; Protein-tyrosine kinase; T790M; Targeted cancer therapy; uncommon EGFR mutation; EGFR mutation; EGFR TKI; T790M; NSCLC; uncommon EGFR mutation
• DOI: 10.1002/ijc.32025
• ISSN: 0020-7136; 1097-0215

Gefitinib, erlotinib and afatinib are approved for first‐line treatment of advanced non‐small cell lung cancer (NSCLC) bearing an activating epidermal growth factor receptor (EGFR) mutation. However, the clinical outcomes among the three EGFR tyrosine kinase inhibitors (TKIs) are still controversial. We aimed to evaluate clinical outcomes and secondary EGFR T790M mutation among the three EGFR TKIs. From May 2014 to January 2016, a total of 301 patients received treatment with gefitinib, erlotinib or afatinib, for first‐line treatment of advanced NSCLC with an activating EGFR mutation, based on their clinicians’ choice. The median overall survival (OS) was 37.0 months. Although the baseline characteristics of patients were unequal, progression‐free survival and OS did not differ among the 3 groups. Multivariate analysis found that gefitinib (adjusted odds ratio [aOR] 3.29, 95% confidence interval [CI], 1.15–9.46, p = 0.027), EGFR TKI treatment duration more than 13 months (aOR 3.16, 95% CI, 1.20–8.33, p = 0.020), male (aOR 3.25, 95% CI, 1.10–9.66, p = 0.034), initial liver metastasis (aOR 4.97, 95% CI 1.18–20.96, p = 0.029) and uncommon EGFR mutation (aOR 0.14, 95% CI, 0.02–0.97, compared to EGFR deletion 19, p = 0.047) were independent factors for secondary T790M mutation. In real‐world practice, choosing first line EGFR TKI based on the patients’ clinical characteristics yielded good clinical outcomes. First‐line gefitinib, longer EGFR TKI treatment duration, male, initial liver metastasis and uncommon EGFR mutations may be independent factors for secondary EGFR T790M mutation. What's new? Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) commonly are used as first‐line therapy for advanced non‐small cell lung cancer (NSCLC). However, the actual extent of their clinical performance, including impacts on secondary EGFR T790M mutation, the most frequent EGFR‐TKI resistance mechanism, remains uncertain. Here, analyses of first‐line EGFR‐TKIs afatinib, erlotinib, gefitinib in advanced EGFR‐mutant NSCLC, with TKIs chosen by clinicians’ discretion, shows median overall survival to be 37 months, which is longer than previously reported. Secondary EGFR T790M mutation was independently associated with multiple factors, including first‐line gefitinib therapy and EGFR TKI use for more than 13 months.