Toshihiko Kaneda1, Akito Hata2, Hiromi Tomioka1, Kosuke Tanaka3, Reiko Kaji3, Shiro Fujita3, Keisuke Tomii4, Nobuyuki Katakami3. 1. Department of Respiratory Medicine, Kobe City Medical Center West Hospital, Kobe, Japan. 2. Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan. Electronic address: a-hata@fbri.org. 3. Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan. 4. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
Abstract
BACKGROUND: Exon 19 deletion mutations (Del-19s) and the exon 21 L858R point mutation are the most common epidermal growth factor receptor (EGFR) mutations. In Del-19, several subtypes actually exist, consisting of the deletional location with or without amino acid insertion/substitution. Little evidence has been described whether the Del-19 subtype affects EGFR-tyrosine kinase inhibitor (TKI) efficacy. METHODS: Between December 2005 and July 2012, we investigated 105 patients harboring a Del-19 who had received EGFR-TKIs. Efficacies of EGFR-TKIs such as response rate (RR), progression-free survival (PFS), and overall survival (OS) were retrospectively evaluated among various patient characteristics. RESULTS: Among these 105 patients with Del-19s, 78 (74%) patients had a deletion from E746 (Del-E746), and 27 (26%) exhibited a deletion from L747 (Del-L747). Median PFS of Del-E746 (11.7 months, 95% confidence interval [CI]: 9.3-15.6) was significantly longer than Del-L747 (10.0 months, 95% CI: 6.4-12.7) (p=0.022). Insertions/substitutions were found in 19 patients (18%), and 91 patients (82%) were without insertions/substitutions. Median PFS without insertions/substitutions (11.7 months, 95% CI 9.3-15.2) was significantly longer than with insertions/substitutions (10.0 months, 95% CI: 4.0-10.6) (p=0.024). No relationships were found for RR among all patient characteristics. In multivariate analysis, performance status (PS) (0/1 vs. 2/3) and initial deletion site (Del-E746 vs. Del-L747) were significant factors for longer PFS, whereas PS, gender (male vs female) and histology (adeno vs squamous) for longer OS. CONCLUSIONS: Our data indicated better efficacy of EGFR-TKI in Del-E746 than Del-L747. Deletional locations may affect EGFR-TKI efficacy.
BACKGROUND: Exon 19 deletion mutations (Del-19s) and the exon 21 L858R point mutation are the most common epidermal growth factor receptor (EGFR) mutations. In Del-19, several subtypes actually exist, consisting of the deletional location with or without amino acid insertion/substitution. Little evidence has been described whether the Del-19 subtype affects EGFR-tyrosine kinase inhibitor (TKI) efficacy. METHODS: Between December 2005 and July 2012, we investigated 105 patients harboring a Del-19 who had received EGFR-TKIs. Efficacies of EGFR-TKIs such as response rate (RR), progression-free survival (PFS), and overall survival (OS) were retrospectively evaluated among various patient characteristics. RESULTS: Among these 105 patients with Del-19s, 78 (74%) patients had a deletion from E746 (Del-E746), and 27 (26%) exhibited a deletion from L747 (Del-L747). Median PFS of Del-E746 (11.7 months, 95% confidence interval [CI]: 9.3-15.6) was significantly longer than Del-L747 (10.0 months, 95% CI: 6.4-12.7) (p=0.022). Insertions/substitutions were found in 19 patients (18%), and 91 patients (82%) were without insertions/substitutions. Median PFS without insertions/substitutions (11.7 months, 95% CI 9.3-15.2) was significantly longer than with insertions/substitutions (10.0 months, 95% CI: 4.0-10.6) (p=0.024). No relationships were found for RR among all patient characteristics. In multivariate analysis, performance status (PS) (0/1 vs. 2/3) and initial deletion site (Del-E746 vs. Del-L747) were significant factors for longer PFS, whereas PS, gender (male vs female) and histology (adeno vs squamous) for longer OS. CONCLUSIONS: Our data indicated better efficacy of EGFR-TKI in Del-E746 than Del-L747. Deletional locations may affect EGFR-TKI efficacy.