Impact of EGFR genotype on the efficacy of osimertinib in EGFR tyrosine kinase inhibitor-resistant patients with non-small cell lung cancer: a prospective observational study

Abstract

Satoshi Igawa,1 Taihei Ono,1 Masashi Kasajima,1 Mikiko Ishihara,1 Yasuhiro Hiyoshi,1 Seiichiro Kusuhara,1 Noriko Nishinarita,1 Tomoya Fukui,1 Masaru Kubota,1 Jiichiro Sasaki,2 Mitsufuji Hisashi,3 Masanori Yokoba,4 Masato Katagiri,4 Katsuhiko Naoki11Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara-city, Kanagawa, Japan; 2Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara-city, Kanagawa, Japan; 3Kitasato University School of Nursing, Sagamihara-city, Kanagawa, Japan; 4School of Allied Health Sciences, Kitasato University, Sagamihara-city, Kanagawa 252-0373, JapanPurpose: A T790M of the epidermal growth factor receptor (EGFR) is the most frequently encountered mutation conferring acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). The aim of this study was to assess the differential clinical outcomes of osimertinib therapy in NSCLC patients with T790M according to the type of activating EGFR mutation, ie, exon 19 deletion or L858R point mutation.Patients and methods: A prospective observational cohort study was conducted to evaluate the efficacy and safety of osimertinib in patients with a major EGFR mutation and T790M-positive advanced NSCLC who had disease progression after first-line EGFR-TKI therapy. The efficacy of osimertinib was evaluated according to the type of EGFR mutation.Results: A total of 51 patients were included in this study. An objective response was obtained in 29 patients, indicating an objective response rate of 58.8%. The response rate was 69.7% in patients with exon 19 deletion and 38.9% in patients with L858R point mutation, indicating a statistically significant difference (P=0.033). The median progression-free survival (PFS) and overall survival (OS) of the entire patient population were 7.8 and 15.5 months, respectively. The median PFS in the exon 19 deletion and L858R point mutation groups was 8.0 months and 5.2 months, respectively, indicating a statistically significant difference (P=0.045). Median OS in the exon 19 deletion and L858R point mutation groups was significantly different at 19.8 months and 12.9 months, respectively (P=0.0015). Multivariate analysis identified the exon 19 deletion as a favorable independent predictor of PFS and OS.Conclusion: Investigators should consider the proportions of sensitive EGFR mutation types as a stratification factor in designing or reviewing clinical studies involving osimertinib.Keywords: EGFR genotype, non-small cell lung carcinoma, osimertinib, efficac