Purpose: Anaplastic lymphoma kinase (ALK ) inhibitors have transformed the management of non-small-cell lung cancer (NSCLC) patients with ALK  gene rearrangement. This paper reports a new resistance mechanism to a second-generation ALK inhibitor, brigatinib.
Case Report: A 43-year-old woman who had no history of smoking was diagnosed with stage IVa (T2bN2M1b) lung adenocarcinoma. After the first-line chemotherapy failed, the patient received crizotinib due to the presence of EML4-ALK  fusion by next-generation sequencing (NGS). The patient had disease progression after 8 months on crizotinib, and a second NGS identified the ALK  G1202R resistance mutation. Therefore, she was switched to brigatinib. After only 53 days of treatment with brigatinib, the patient developed a new 1.6× 1.2 cm lesion in the mediastinal lymph node. A third NGS testing revealed a new form of NTRK  rearrangement (LIPI-NTRK1 ). The patient died 16 months after diagnosis.
Conclusion: This paper provides new insights into the primary resistance to brigatinib in NSCLC patients carrying ALK  G1202R mutation. The new fusion form of NTRK rearrangement was detected, which may provide potential treatment options after brigatinib resistance.
Keywords: NTRK1, ALK, primary resistance, brigatinib, NSCLC