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

TL;DR

A lung cancer patient resistant to alectinib showed partial response to pralsetinib after developing a KIF5B-RET fusion.

Contribution

Identifies KIF5B-RET fusion as a resistance mechanism to alectinib and suggests pralsetinib as a treatment option.

Findings

Patient developed KIF5B-RET fusion after alectinib treatment.

Pralsetinib treatment led to a partial response lasting 4 months.

Highlights RET inhibition as a potential strategy for resistance management.

Abstract

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

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