Acquired EGFR L858R mutation following ALK-TKI resistance in lung adenocarcinoma: a case report

TL;DR

A patient with lung cancer developed resistance to ALK-TKI treatment and acquired an EGFR mutation, suggesting a new resistance mechanism.

Contribution

This case report identifies EGFR L858R mutation as a novel resistance mechanism following ALK-TKI treatment in lung adenocarcinoma.

Findings

A patient with ALK fusion lung cancer developed resistance to ALK-TKIs and acquired EGFR L858R and ALK F1174L mutations.

Switching to third-generation EGFR-TKI treatment was effective after resistance to ALK-TKIs.

The case highlights the importance of re-biopsy for identifying targetable resistance mechanisms.

Abstract

Reports of secondary mutations in mutual exclusive driver genes after resistance to targeted therapy are rare. We present a patient with Anaplastic lymphoma kinase (ALK) fusion lung adenocarcinoma who received sequential treatment with ALK tyrosine kinase inhibitor (TKI) (crizotinib, PFS:32.3 months and then conteltinib, PFS: 29 months). Upon further disease progression, a lung biopsy and next-generation sequencing (NGS) revealed acquired secondary driver mutations including Epidermal Growth Factor Receptor (EGFR) L858R and ALK mutation of F1174L. Subsequently, the patient switched to third generation EGFR-TKI treatment with almonertinib. This case suggests EGFR mutation is one of the mechanisms of ALK-TKI resistance, highlights the value of re-biopsy in identifying potentially targetable resistance mechanisms and underscores the spatiotemporal heterogeneity of tumors under the selective pressure of ALK-TKI.

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