Coexistence of a secondary STRN-ALK, EML4-ALK double-fusion variant in a lung adenocarcinoma patient with EGFR mutation: a case report.

Abstract

ALK-positive disease is characterized by the presence of ALK gene rearrangements that encode driver fusion oncoproteins. EML4-ALK fusion is regarded as the most common type in advanced nonsmall cell lung cancers. STRN-ALK is a novel ALK fusion partner in NSCLC and is considered sensitive to targeted therapy. However, there was no study regarding effective therapy for EML4-ALK and STRN-ALK double fusion variants in EGFR-resistant mutant lung cancer. TP53, RB1, and EGFR exon 21 L858R were found in tumor tissues and plasma from patients with capture-based NGS. After 3 months of gefitinib treatment, an NGS of plasma circulating tumor DNA showed that all variants disappeared significantly, and the tumor mass regressed on CT. However, after 10 months, the patient developed drug resistance and the disease progressed with the appearance of new metastatic lesions in the liver and bones. A repeated NGS test revealed EGFR exon20 T790M and the appearance of a novel double-fusion EML4-ALK and STRN-ALK. A combined therapeutic regimen of crizotinib plus osimertinib showed a promising prognosis confirmed with lung CT scans showing stable lesions without any new metastasis. Moreover, a subsequent genotype by NGS also showed the disappearance of STRN-ALK and EGFR exon20 T790M. The therapeutic efficacy of crizotinib plus osimertinib on EML4-ALK and STRN-ALK double-fusion variant in patients with EGFR-resistant mutant lung cancer may provide a supportive reference for the patients with such genetic alteration.

• Authors: Qian Zeng, Han Gao, Longdan Zhang, Shouming Qin, Yongyao Gu, Quanfang Chen
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 32 Issue 8 Pg. 890-893 (09 01 2021) ISSN: 1473-5741 [Electronic] England
• PMID: 34232939 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• Acrylamides
• Aniline Compounds
• Calmodulin-Binding Proteins
• Cell Cycle Proteins
• Membrane Proteins
• Microtubule-Associated Proteins
• Nerve Tissue Proteins
• Protein Kinase Inhibitors
• STRN protein, human
• osimertinib
• Crizotinib
• ALK protein, human
• Anaplastic Lymphoma Kinase
• ErbB Receptors
• EML4 protein, human
• Serine Endopeptidases
• Gefitinib

Topics

• Acrylamides (therapeutic use)
• Adult
• Anaplastic Lymphoma Kinase (genetics)
• Aniline Compounds (therapeutic use)
• Calmodulin-Binding Proteins (genetics)
• Cell Cycle Proteins (genetics)
• Crizotinib (therapeutic use)
• ErbB Receptors (genetics)
• Gefitinib (therapeutic use)
• Humans
• Lung Neoplasms (drug therapy, genetics)
• Male
• Membrane Proteins (genetics)
• Microtubule-Associated Proteins (genetics)
• Nerve Tissue Proteins (genetics)
• Protein Kinase Inhibitors (therapeutic use)
• Serine Endopeptidases (genetics)