Journal
ANTI-CANCER DRUGS
Volume 32, Issue 8, Pages 890-893Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CAD.0000000000001094
Keywords
crizotinib; double-fusion; EML4-ALK; gefitinib; osimertinib; STRN-ALK
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Funding
- Natural Science Foundation of Guangxi Province [2017GXNSFAA198087]
- Guangxi medical and health suitable technology development project [S2017037, Z20180927]
- First Affiliated Hospital of Guangxi Medical University
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The study found a patient with EGFR-resistant mutant lung cancer who developed a double-fusion EML4-ALK and STRN-ALK variant after gefitinib treatment, but a combined therapeutic regimen of crizotinib plus osimertinib showed a promising prognosis, confirmed with disappearance of some genes in subsequent genotype testing.
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.
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