Effective response to crizotinib of concurrent KIF5B-MET and MET-CDR2-rearranged non-small cell lung cancer: A case report

Abstract

BACKGROUND 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. CASE SUMMARY 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. CONCLUSION 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.

Identification of MET fusions as novel therapeutic targets sensitive to MET inhibitors in lung cancer

“…In addition, chemotherapy plus bevacizumab may benefit patients harboring sensitive EGFR mutations and acquired MET amplifications after the failure of EGFR-TKI treatment. In this study, we collected the published cases [14][15][16][17][18][19][20] of patients harboring MET fusions, and the findings cast new light on the role of crizotinib in benefiting these patients. The findings suggested that crizotinib as a single agent can serve as a suitable treatment option for patients harboring primary MET fusions, and combined therapy with crizotinib and EGFR-TKIs could significantly benefit patients with EGFR mutations also harboring acquired MET fusions after the development of resistance to EGFR-TKIs.…”

“…Immunotherapy is another treatment option for NSCLC patients with MET alterations [11][12][13]. Recently, a series of reports revealed novel detectable alterations of MET, MET fusions, which are involved in the development of lung cancer and exhibit a special response to the given treatment [14][15][16][17][18][19][20]. However, MET fusions are rare in lung cancer, and a systematic analysis of patients harboring this kind of genomic alteration is lacking.…”

Clinical characteristics and targeted therapy of different gene fusions in non-small cell lung cancer: a narrative review

“…The patient had displayed a PR to crizotinib (37). Previous cases have also shown the efficacy of crizotinib in NSCLC patients with MET fusions (68)(69)(70). In September 2018, Zhu et al reported the first case of EGFR-TKI-resistant MET-UBE2H fusion in a patient with LUAD.…”

Case report: Acquired resistance to crizotinib from a MET Y1230H mutation in a patient with non-small cell lung cancer and KIF5B-MET fusion

“…The most common MET aberrations are gene amplifications and exon 14 splice variants. MET fusion is a rare type of structural rearrangement; nine MET fusion partner genes have been identified, namely: PRKAR2B ( 1 ), KIF5B ( 2 – 4 ), STARD3NL ( 5 ), CDR2 ( 6 ), UBE2H ( 7 ), HLA-DRB1 ( 8 ), ATXN7L1 ( 9 ), CD47 ( 10 ), and SPECC1L ( 11 ). To date, eight cases of KIF5B -MET gene fusion have been reported in the literature, of which only a few have described the efficacy of crizotinib ( Table 1 ).…”