Heterogeneity response to afatinib in gastric cancer patient with uncommon epidermal growth factor receptor (EGFR) mutations: a case report

Despite concerted efforts that have been made to characterize and understand the genomic landscape of gastric cancer (GC), only HER2 has been validated as a molecular target for GC treatment. Identifying new valid therapeutic targets is important for the treatment of this disease. The present report describes a Chinese male with a history of smoking two packs per day, who did not have a family history of cancer or other hereditary diseases, we discovered a small painless lump in the right groin in February 2018. Histopathology revealed a primary gastric adenocarcinoma. Positron emission tomography-computed tomography (PET-CT) showed multiple hypermetabolic nodules in the right upper lung, greater curvature of the stomach, and muscles. The patient had received treatment included oxaliplatin, docetaxel, and tegafur for two cycles, and second-line therapy of irinotecan and capecitabine, inguinal mass excision followed by concurrent radio-chemotherapy. However, the disease rapidly progressed. Whole exome sequencing (WES) showed uncommon epidermal growth factor receptor (EGFR) mutation of G719S + L861Q. The following EGFR tyrosine kinase inhibitors (TKIs) afatinib demonstrated partial response. Two months after targeted therapy, gastroscopy indicated rapid progression. With subsequent gastric specimen WES analysis, secondary MET amplification was found. The patient received local radiotherapy for gastric lesions as well as oral administration of apatinib. However, the disease rapidly progressed. A month later, he died of hepatic encephalopathy caused by obstructive jaundice combined with pulmonary and biliary tract infection. The present study indicated that afatinib might be a beneficial therapeutic option for a subset of GC patients with rare EGFR mutation in their tumors.