Case Report: Successful late-line pralsetinib treatment in an ALK-rearranged lung adenocarcinoma patient with KIF5B-RET fusion resistant to alectinib

Anaplastic lymphoma kinase (<i>ALK</i>) fusion, an oncogenic driver alteration, accounts for 5%-6% of non-small cell lung cancer (NSCLC) patients. <i>ALK</i> tyrosine kinase inhibitors (TKIs) provide significant clinical benefit in advanced ALK-rearranged NSCLC. However, acquired resistance to <i>ALK</i> TKIs inevitably arises, and the underlying mechanisms remain incompletely elucidated. This report describes a stage IV lung adenocarcinoma (LUAD) patient with <i>ALK</i>-rearranged who developed <i>KIF5B-RET</i> fusion-mediated resistance following second-line alectinib therapy. The patient achieved a partial response (PR) to third-line pralsetinib, sustained for 4 months. This case highlights <i>KIF5B-RET</i> fusion as a potential resistance mechanism post alectinib treatment and suggested = pralsetinib, a <i>RET</i> inhibitor, as a viable therapeutic option in this context. These findings contribute to the evolving understanding of resistance management strategies in <i>ALK</i>-rearranged NSCLC.