Tomoyuki Otsuka1, Masahide Mori2, Yukihiro Yano3, Junji Uchida4, Kazumi Nishino4, Reiko Kaji5, Akito Hata5, Yoshihiro Hattori6, Yoshiko Urata6, Toshihiko Kaneda7, Motoko Tachihara8, Fumio Imamura4, Nobuyuki Katakami5, Shunichi Negoro9, Satoshi Morita10, Soichiro Yokota3. 1. Department of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan Department of Respiratory Medicine, Allergy, and Rheumatic Diseases, Osaka University Graduate School of Medicine, Suita, Japan. 2. Department of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan mmori@toneyama.go.jp. 3. Department of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan. 4. Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. 5. Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan. 6. Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan. 7. Department of Respiratory Medicine, Kobe City Medical Center West Hospital, Kobe, Japan. 8. Department of Respiratory Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. 9. Department of Medical Oncology, Hyogo Cancer Center, Akashi, Japan. 10. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Abstract
AIM: Non-small cell lung cancer (NSCLC) with minor mutations in the epidermal growth factor receptor (EGFR) gene, except for the common 15 base-pair deletions in exon 19 and the L858R mutation in exon 21, is rare, and only few data exist on this patient population. The aim of the present study was to describe the clinical characteristics and to clarify the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) in patients with NSCLC harboring minor mutations of the EGFR gene. PATIENTS AND METHODS: This was a multicenter, retrospective study that analyzed specimens from patients with NSCLC who had minor EGFR gene mutations and were treated with EGFR-TKIs between June 2002 and March 2012. RESULTS: Out of 56 patients with minor mutations of the EGFR gene, 44 were treated with either gefitinib or erlotinib. Mutation sites were G719X in exon 18 (n=35), L861Q in exon 21 (n=11), and G874S in exon 21 (n=1). Three patients had both the G719S and the L861Q mutation. The response rate to TKI treatment was 29.5%, and the disease control rate was 63.6%. The median progression-free survival (PFS) was 6.7 months [95% confidence interval (CI)=2.06-8.66 months]. The median PFS was 7.2 months (95% CI=4.23-12.3 months) in 32 patients who received first- or second-line treatment with EGFR-TKIs, whereas the median PFS was 1.57 months (95% CI=0.73-3.8 months) in 12 patients treated with EGFR-TKIs as a third-line or later treatment. In multivariate Cox analysis, erlotinib therapy was associated with a longer PFS than gefitinib (p=0.025). CONCLUSION: Patients with NSCLC harboring minor mutations of the EGFR gene exhibited a modest response to EGFR-TKI treatment. Treatment with first-generation EGFR-TKIs, in particular erlotinib, may be considered a first- or second-line option for patients with NSCLC with minor EGFR mutations. Copyright
AIM: Non-small cell lung cancer (NSCLC) with minor mutations in the epidermal growth factor receptor (EGFR) gene, except for the common 15 base-pair deletions in exon 19 and the L858R mutation in exon 21, is rare, and only few data exist on this patient population. The aim of the present study was to describe the clinical characteristics and to clarify the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) in patients with NSCLC harboring minor mutations of the EGFR gene. PATIENTS AND METHODS: This was a multicenter, retrospective study that analyzed specimens from patients with NSCLC who had minor EGFR gene mutations and were treated with EGFR-TKIs between June 2002 and March 2012. RESULTS: Out of 56 patients with minor mutations of the EGFR gene, 44 were treated with either gefitinib or erlotinib. Mutation sites were G719X in exon 18 (n=35), L861Q in exon 21 (n=11), and G874S in exon 21 (n=1). Three patients had both the G719S and the L861Q mutation. The response rate to TKI treatment was 29.5%, and the disease control rate was 63.6%. The median progression-free survival (PFS) was 6.7 months [95% confidence interval (CI)=2.06-8.66 months]. The median PFS was 7.2 months (95% CI=4.23-12.3 months) in 32 patients who received first- or second-line treatment with EGFR-TKIs, whereas the median PFS was 1.57 months (95% CI=0.73-3.8 months) in 12 patients treated with EGFR-TKIs as a third-line or later treatment. In multivariate Cox analysis, erlotinib therapy was associated with a longer PFS than gefitinib (p=0.025). CONCLUSION:Patients with NSCLC harboring minor mutations of the EGFR gene exhibited a modest response to EGFR-TKI treatment. Treatment with first-generation EGFR-TKIs, in particular erlotinib, may be considered a first- or second-line option for patients with NSCLC with minor EGFR mutations. Copyright
Authors: Kevin G Neill; James Saller; Sameer Al Diffalha; Barbara A Centeno; Mokenge P Malafa; Domenico Coppola Journal: Cancer Genomics Proteomics Date: 2018 May-Jun Impact factor: 4.069