Sustained Complete Response to Brigatinib in a Young Patient With ALK-Positive NSCLC Harboring I1171N Mutation Post-Alectinib Resistance.

Abstract

ALK-rearranged non-small cell lung cancer (NSCLC) represents a paradigm of precision oncology, but acquired resistance to second-generation ALK tyrosine kinase inhibitors (TKIs) such as alectinib remains inevitable. We report a young, nonsmoker male with ALK-positive metastatic NSCLC who achieved a sustained complete response (CR) to brigatinib following alectinib resistance mediated by the ALK I1171N mutation. After 22 months of response to alectinib, disease progression prompted repeat molecular profiling, which identified the I1171N alteration. Brigatinib was initiated, and a complete radiologic response was documented within 3 months and has been sustained for over 12 months, including durable intracranial disease control. Sustained CR in I1171N-mediated alectinib resistance is rare and highlights the critical role of repeat molecular testing to guide ALK TKI sequencing.