BACKGROUND: Somatic mutations in the epidermal growth factor receptor (EGFR) gene are a predictor of response to treatment with EGFR tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, mechanisms of de novo resistance to these drugs in patients harboring EGFR mutations have remained unclear. We examined whether the mutational status of KRAS might be associated with primary resistance to EGFR-TKIs in EGFR mutation-positive patients with NSCLC. METHODS: Forty patients with NSCLC with EGFR mutations who were treated with gefitinib or erlotinib and had archival tissue specimens available were enrolled in the study. KRAS mutations were analyzed by direct sequencing. RESULTS: Three (7.5%) of the 40 patients had progressive disease, and two (67%) of these three individuals had both KRAS and EGFR mutations. CONCLUSIONS: Our results suggest that KRAS mutation is a negative predictor of response to EGFR-TKIs in EGFR mutation-positive patients with NSCLC.
BACKGROUND: Somatic mutations in the epidermal growth factor receptor (EGFR) gene are a predictor of response to treatment with EGFR tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, mechanisms of de novo resistance to these drugs in patients harboring EGFR mutations have remained unclear. We examined whether the mutational status of KRAS might be associated with primary resistance to EGFR-TKIs in EGFR mutation-positive patients with NSCLC. METHODS: Forty patients with NSCLC with EGFR mutations who were treated with gefitinib or erlotinib and had archival tissue specimens available were enrolled in the study. KRAS mutations were analyzed by direct sequencing. RESULTS: Three (7.5%) of the 40 patients had progressive disease, and two (67%) of these three individuals had both KRAS and EGFR mutations. CONCLUSIONS: Our results suggest that KRAS mutation is a negative predictor of response to EGFR-TKIs in EGFR mutation-positive patients with NSCLC.
Authors: King Pan Ng; Axel M Hillmer; Charles T H Chuah; Wen Chun Juan; Tun Kiat Ko; Audrey S M Teo; Pramila N Ariyaratne; Naoto Takahashi; Kenichi Sawada; Yao Fei; Sheila Soh; Wah Heng Lee; John W J Huang; John C Allen; Xing Yi Woo; Niranjan Nagarajan; Vikrant Kumar; Anbupalam Thalamuthu; Wan Ting Poh; Ai Leen Ang; Hae Tha Mya; Gee Fung How; Li Yi Yang; Liang Piu Koh; Balram Chowbay; Chia-Tien Chang; Veera S Nadarajan; Wee Joo Chng; Hein Than; Lay Cheng Lim; Yeow Tee Goh; Shenli Zhang; Dianne Poh; Patrick Tan; Ju-Ee Seet; Mei-Kim Ang; Noan-Minh Chau; Quan-Sing Ng; Daniel S W Tan; Manabu Soda; Kazutoshi Isobe; Markus M Nöthen; Tien Y Wong; Atif Shahab; Xiaoan Ruan; Valère Cacheux-Rataboul; Wing-Kin Sung; Eng Huat Tan; Yasushi Yatabe; Hiroyuki Mano; Ross A Soo; Tan Min Chin; Wan-Teck Lim; Yijun Ruan; S Tiong Ong Journal: Nat Med Date: 2012-03-18 Impact factor: 53.440
Authors: Nikhil Wagle; Caroline Emery; Michael F Berger; Matthew J Davis; Allison Sawyer; Panisa Pochanard; Sarah M Kehoe; Cory M Johannessen; Laura E Macconaill; William C Hahn; Matthew Meyerson; Levi A Garraway Journal: J Clin Oncol Date: 2011-03-07 Impact factor: 44.544