P1-16-5 - A Case of Lung Adenocarcinoma Resistant to Crizotinib Harboring Kras Mutation and Eml4-Alk Fusion Gene

Abstract

Background: The echinoderm microtubule-associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) fusion gene in lung cancer is mutually exclusive with epidermal growth factor receptor (EGFR) and KRAS mutations. If EGFR or KRAS gene mutations have been detected, it is unlikely that EML4-ALK fusion gene will be present in the same patient. We report a case of lung adenocarcinoma resistant to crizotinib harboring KRAS mutation and EML4-ALK fusion gene.Case presentation: A 54-year-old female non-smoker underwent right middle and lower lobectomy for stage IIIA lung adenocarcinoma in January 2006. Pathological diagnosis was mucinous bronchoalveolar carcinoma, and she received 4 cycles of adjuvant chemotherapy (carboplatin + paclitaxel). The patient relapsed in January 2007, presenting with multiple lung metastases. Despite gefitinib treatment from February 2007, the cancer continued to progress, and she received 4 cycles of docetaxel beginning in April 2007, erlotinib beginning in February 2008, 13 cycles of TS-1 beginning in May 2008 and 19 cycles of pemetrexed (combined with 4 cycles of bevacizumab). EGFR gene mutation was negative and mutant KRAS codon 12 was positive in genetic diagnosis. She hoped crizotinib treatment then we assessed EML4-ALK fusion gene using FFPE from resected specimen by RT-PCR and sequencing assay. A variant 1 of EML4-ALK fusion gene was identified. The patient was treated by crizotinib, but her disease progressed after 42 days of therapy.Discussion: To our knowledge, this is the first case report of a patient resistant to crizotinib harboring KRAS mutation and EML4-ALK fusion gene in Japan. KRAS mutation in addition to EML4-ALK fusion gene may cause the resistance to crizotinib.