Limited effect of afatinib in a non-small cell lung cancer patient harboring an epidermal growth factor receptor K860I missense mutation: A case report

Abstract

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are key drugs in the treatment of non-small cell lung cancer (NSCLC) patients with EGFR mutations; however, first-generation EGFR-TKIs, such as gefitinib and erlotinib, are not effective in patients with uncommon EGFR mutations. In contrast, efficacy of afatinib has been reported in some types of uncommon EGFR mutation such as G710X, L861Q. The effect of afatinib in NSCLC patients with the EGFR K860I mutation has been shown in vitro, but its clinical efficacy has not been demonstrated. Here, we report the experience of afatinib administration in an NSCLC patient with an EGFR K860I mutation. A 69-year-old woman presented with right hemiplegia and dysarthria. Multiple brain and lung tumors were observed. She underwent craniotomy and was diagnosed with lung adenocarcinoma. After stereotactic brain radiation therapy, cisplatin, pemetrexed, and bevacizumab combination therapy was initiated. Unfortunately, she was unable to continue chemotherapy as she had an intestinal perforation after two cycles. After five months, recurrence of multiple brain metastases and an increase in primary lung cancer were confirmed. Next-generation sequencing (NGS) was performed in a clinical trial, and an EGFR K860I mutation was detected in her tumor. Afatinib was administered and the primary lung tumor shrank, but multiple brain metastases were exacerbated. After irradiation of the brain, afatinib administration was continued. In conclusion, afatinib may show an effect in NSCLC patients with the EGFR K860I mutation, but its efficacy is limited.

Keywords: K860I; afatinib; brain metastasis; epidermal growth factor receptor uncommon mutation; second-generation EGFR-tyrosine kinase inhibitors.