Published online Mar 16, 2022. doi: 10.12998/wjcc.v10.i8.2529
Peer-review started: August 26, 2021
First decision: October 29, 2021
Revised: November 12, 2021
Accepted: February 10, 2022
Article in press: February 10, 2022
Published online: March 16, 2022
Due to the rarity of mesenchymal-epithelial transition factor (MET) fusions, the clinical efficacy of crizotinib has only been described in a few patients with MET fusions involving various fusion partners. Herein, we report the clinical response to crizotinib of a patient with advanced poorly differentiated non-small cell carcinoma (NSCLC) having concurrent MET fusions.
A 46-year-old woman was diagnosed with poorly differentiated NSCLC (T4N3M1). With no classic driver mutations, she was treated with two cycles of gemcitabine and cisplatin without clinical benefit. Targeted sequencing revealed the detection of two concurrent MET fusions, KIF5B-MET and novel MET-CDR2. Crizotinib was initiated at a dose of 250 mg twice daily. Within 4 wk of crizotinib therapy, repeat computed chromatography revealed a dramatic reduction in primary and metastatic lesions, assessed as partial response. She continued to benefit from crizotinib for 3 mo until disease progression and died within 1 mo despite receiving nivolumab therapy.
Crizotinib sensitivity was observed in an advanced poorly differentiated NSCLC patient with concurrent MET fusions KIF5B-MET and MET-CDR2. Crizotinib can serve as a therapeutic option for patients with MET fusions. In addition, our case also highlights the importance of comprehensive genomic profiling particularly in patients with no classic driver mutation for guiding alternative therapeutic decisions.
Core Tip: The most common mesenchymal-epithelial transition factor (MET) gene aberrations are gene amplifications and exon 14 splice variants found in approximately 2% to 10% of lung cancer patients. Chromosomal rearrangements resulting in gene fusions involving MET are generally rare but could account for MET-driven oncogenesis. The rarity and diversity of MET fusions in non-small cell lung cancer (NSCLC) limit the volume of evidence documenting the clinical efficacy of crizotinib in treating MET-rearranged NSCLC patients. Herein, we report the clinical response to crizotinib of a patient with advanced poorly differentiated NSCLC harboring concurrent MET-involving rearrangements, including a novel MET-CDR2 gene fusion.