Case report: Durable response to afatinib in a patient with lung cancer harboring two uncommon mutations of EGFR and a KRAS mutation. (November 2016)

• Record Type: Journal Article
• Authors: Tanizaki, Junko; Banno, Eri; Togashi, Yosuke; Hayashi, Hidetoshi; Sakai, Kazuko; Takeda, Masayuki; Kaneda, Hiroyasu; Nishio, Kazuto; Nakagawa, Kazuhiko
• Is Part Of: Lung cancer. Volume 101(2016)
• Page Start: 11
• Page End: 15
• Publication Date: 2016-11
• Subjects: EGFR mutation -- KRAS mutation -- Afatinib -- Non–small cell lung cancer -- Tyrosine kinase inhibitor; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2016.09.001
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: We report a case of NSCLC with EGFR mutations G719C, S768I and KRAS E49 K mutation. Treatment with afatinib resulted in a decrease of the patient's serum CEA level. Afatinib was clinically effective for this patient as confirmed by PET-CT. Efficacy of afatinib for EGFR(S768I) was observed by in vitro assay as well. Abstract: Comprehensive genomic profiling for non–small cell lung cancer (NSCLC) is likely to identify more patients with rare genetic alterations including uncommon epidermal growth factor receptor gene ( EGFR ) mutations. It remains unclear how such patients should be treated, however. We here report a case of NSCLC positive for two uncommon mutations of EGFR and a KRAS mutation, including its treatment with the second-generation EGFR tyrosine kinase inhibitor (TKI) afatinib. Tumor specimen obtained by a NSCLC patient with no smoking history was analyzed by next-generation sequencing. Comprehensive genomic profiling revealed that the patient harbored the EGFR mutations G719C and S768I as well as the E49K mutation of KRAS . Treatment with afatinib was clinically effective as confirmed by PET-CT scans of bone metastases and by a marked decrease in the serum concentration of carcinoembryonic antigen. Afatinib was the most effective among seven EGFR-TKIs tested in inhibiting the growth of Ba/F3 cells expressing EGFR(S768I), showing an efficacy similar to that apparent with cells expressing the common EGFR mutant L858R, whereas first- and third-generation EGFR-TKIs were markedly less effective against EGFR(S768I) than against EGFR(L858R). These data suggest that EGFR-TKIs differ in their activity toward cells expressing EGFR(S768I) in vitro. Consistently, afatinib was clinically effective for the treatment of NSCLC harboring G719C and S768I mutations of EGFR . Further studies are warranted to determine the most appropriate EGFR-TKI for treatment of NSCLC harboring uncommon EGFR mutations.