A durable response to savolitinib in a patient with lung adenocarcinoma harboring two novel MET exon 14 skipping sites.

MET exon 14 ( METex14 ) skipping variants are oncogenic drivers in non-small-cell lung cancer. Several METex14 skipping alterations have been identified, but different mesenchymal-epithelial transition (MET) exon splicing variants tend to present different clinical outcomes. Here, we reported that a patient with lung adenocarcinoma harbored two novel METex14 skipping mutations (c.2888-35_2888-16del and c.2888-4T>G) identified by the tissue-based next-generation sequencing (NGS) and received savolitinib treatment after chemotherapy failed with brain metastasis. The patient responded well to savolitinib until disease progression in brain lesions and achieved a progress-free survival (PFS) of over 19.7 months. Considering the durable response for extracranial lesions and the same METex14 skipping sites identified by circulating tumor DNA-based NGS, the patient was still given savolitinib combined with stereotactic body radiation therapy for brain lesions. An extracranial PFS of 28 months was achieved. This is the first report of a patient with lung adenocarcinoma harboring two novel METex14 skipping mutations that responded to the MET inhibitor savolitinib. Our case may provide evidence for the treatment of patients with two novel METex14 skipping variants and offer a therapy regimen for those with intracranial progression.