Remarkable Efficacy of Capmatinib in a Patient with Cancer of Unknown Primary with MET Amplification

Abstract

This case report describes a 70-year-old female with cancer of unknown primary origin (CUP) who exhibited multiple distant lymph node metastases. Despite conventional chemotherapy (carboplatin and paclitaxel) and immunotherapy (nivolumab), disease progression was noted. Genomic profiling revealed MET amplification, leading to the administration of capmatinib, a selective MET tyrosine kinase inhibitor. The patient experienced substantial tumor reduction with dose adjustments due to adverse effects, indicating the potential efficacy of capmatinib in treating CUP with MET amplification.

Keywords: MET amplification; MET exon 14 skipping; MET inhibitors; cancer of unknown primary; capmatinib.

Figure 1.

Comparison of computed tomography scans of the left cervical lymph nodes before and after treatment. The pretreatment lesion (a, yellow arrow) appears substantially reduced one month after commencing capmatinib therapy (b, yellow arrow). A remarkable reduction was observed in March 2024, as indicated by the yellow arrow in (c). PET-CT from January 2023 prior to treatment showed lymph node enlargement with abnormal fluorodeoxyglucose (FDG) radiotracer accumulation in the left axillary, supraclavicular, neck, and abdominal regions. No other abnormal organ-specific FDG uptake was observed (d). PET-CT: positron emission tomography-computed tomography

Figure 2.

Pathological findings in the axillary and cervical lymph nodes [Hematoxylin and Eosin (H&E) staining]. Representative images show the proliferation of atypical cells, which appear ovoid with prominent nucleoli forming alveolar patterns. Immunohistochemical staining showed positive markers, including CK7, CK19, CK20 (p+), CDX2 (p+), WT-1 (p+), PgR (p+), and HER2 (1-2+), along with negative markers TTF-1, GCDFP15, mammaglobin, ER, p40, PAX8, GATA3, synaptophysin, β-catenin, and D2-40 [bars; H&E staining (left): 1 mm, others: 100 μm].

Figure 3.

Gross comparison of lesions before and after treatment. Enlargement of the lymph nodes on the left side of the neck is visibly reduced when observed externally (red arrow) (a: before treatment, b: 5 months after initiating capmatinib treatment).