Osimertinib, a third-generation
epidermal growth factor receptor (EGFR)
tyrosine kinase inhibitor (TKI), shows great clinical activity in
non-small cell lung cancer (NSCLC) patients with EGFR mutations regardless of T790M mutation at first-line
chemotherapy. Previous studies demonstrated that there are few patients with initial resistance to
osimertinib. Here, we describe a case to report the efficacy of
afatinib in an EGFR-mutated NSCLC patient with early progression to first-line
osimertinib treatment. A 68-year-old Japanese male was diagnosed with stage IVB
lung adenocarcinoma with the EGFR L858R mutation in exon 21. Two months after the start of
osimertinib, his
tumor progressed at the initial response evaluation. Because he refused to receive cytotoxic
chemotherapy,
afatinib treatment was initiated. He was administered
afatinib, and the
tumor shrank. After five months of
afatinib treatment, nevertheless the primary
tumor was not enlarged, he experienced
disease progression with leptomeningeal
metastasis and passed away. To elucidate the resistance mechanisms of
osimertinib in this patient, we performed next-generation sequencing (NGS) on
tumor samples from
pleural effusions after
osimertinib failure. NGS revealed no specific gene mutations causing resistance to
osimertinib except for the EGFR L858R mutation; however, his
tumor had a relatively high
tumor mutational burden.
Afatinib is considered an option for EGFR-mutated patients with early progression to
osimertinib.