Rare Synchronous Lung Cancers in a Nonsmoker with Epidermal Growth Factor Receptor and Mesenchymal-Epithelial Transition Alterations: A Case Report.

Lung cancer is the second most common cancer; however, synchronous lung cancer is rare and challenging to treat. We report the case of an 80-year-old female patient who presented with two lung lesions with primary tumor characteristics, which revealed squamous cell carcinoma and synchronous adenocarcinoma after histological sampling. Next-generation sequencing (NGS) analysis revealed a MET Exon 14 skipping mutation in squamous cell carcinoma and an epidermal growth factor receptor mutation in adenocarcinoma. Capmatinib and stereotactic radiotherapy were initiated for the adenocarcinoma with a good clinical response. Capmatinib treatment had to be discontinued because of stage 3 edema of the lower limbs, after which a left lobectomy was performed. Currently, the patient is considered to be in remission. This case highlights the need for histological analysis of every lung lesion with primary tumor characteristics, as well as for NGS analysis in search of specific mutations enabling the introduction of targeted therapies. mesenchymal-epithelial transition.

Baer X ，Chevallier M ，Rey Cobo J ，Plojoux J ，De Vito C ，Addeo A ... -  《Case Reports in Oncology》

Synchronous Double Primary Lung Adenocarcinomas With EGFR L858R Point Mutation and MET Exon 14 Skipping Mutation.

Ando S ，Futami S ，Azuma K ，Nishimatsu K ，Shirasaka T ，Minami S ... -  《-》

Capmatinib in MET Exon 14 Skipping Mutation-Positive Lung Adenocarcinoma with Extensive Central Nervous System Metastasis.

Several selective mesenchymal-epithelial transition (MET) inhibitors have recently demonstrated favorable systemic efficacy in MET exon 14 skipping mutation-positive non-small cell lung cancer. However, there are limited data on their efficacy against central nervous system (CNS) metastasis, especially leptomeningeal seeding. Recently, we encountered a case of a 65-year-old woman who was diagnosed with metastatic lung adenocarcinoma. As routine molecular testing showed no genomic alterations, including epidermal growth factor receptor mutation and anaplastic lymphoma kinase translocation, the patient received a frontline platinum-doublet followed by paclitaxel. However, the tumor did not respond to these therapies, and her condition became deleterious owing to extensive brain and leptomeningeal metastases. Plasma genotyping revealed that the tumor harbored a MET exon 14 skipping mutation, and we started capmatinib, a selective MET inhibitor. The CNS lesions markedly decreased and the performance status of the patient dramatically improved. Our report highlights the significant CNS activity of capmatinib, even in cases of leptomeningeal metastasis. In addition, this report emphasizes the importance of the active utilization of molecular profiling to detect rare but druggable genetic alterations for the better management of patients with lung cancer.

Kim TW ，Lee KM ，Lee SH 《-》

Responses to crizotinib and cabozantinib in patient with lung adenocarcinoma harboring mesenchymal-epithelial transition factor exon 14 skipping mutation: A case report.

Lung cancer is a leading cause of cancer-related mortality worldwide. Currently, targeted therapy has proved highly efficient in the treatment of advanced non-small cell lung cancer (NSCLC). Mesenchymal-epithelial transition factor (MET) is considered a validated molecular target in NSCLC. Given the low incidence of MET exon 14 skipping mutation, the planning of precision treatment for patients is a clinical problem that needs to be solved. In this report, we present a MET-positive case that benefited from crizotinib and cabozantinib treatment. A 77-year-old patient was diagnosed with lung adenocarcinoma in our hospital. Positron emission tomography-computed tomography (PET-CT) showed a right upper lobe mass (58 × 56 mm, SUVmax 15.6), right hilar enlarged lymph nodes, and multiple bone and left adrenal metastases (c-T3N1M1c). MET exon 14 mutation (exon14, c.2888-1G>C) was examined using the lung puncture sample by next generation sequencing. Therefore, the patient was diagnosed with late-stage lung adenocarcinoma with MET exon14 skipping gene mutation. Crizotinib was given as the first-line treatment from August 2019. Considering the resistance of crizotinib, cabozantinib was given for second-line treatment. Crizotinib was administered (250 mg bid) for 8 months, and her disease achieved partial regression (PR) and progression-free survival (PFS), which lasted for 8 months. The patient also reached PR after the second-line treatment with cabozantinib, and is currently under follow-up, with an overall survival (OS) of >12 months. As MET exon 14 skipping mutation is rare in clinical practices, MET-TKIs (tyrosine kinase inhibitors) treatment can boost curative effects and improve prognosis of patients with advanced lung adenocarcinoma. This case report supports a rationale for the treatment of lung adenocarcinoma patients with a MET exon 14 skipping mutation and provides alternative treatment options for these types of NSCLC patients.

Qin RY ，Liu LS ，Zhang HY ，Lu CH ，Guo XY ，Zhang LY ，Yuan XB ，Xue HH ... -  《-》

Capmatinib‑associated interstitial lung disease in a patient with lung adenocarcinoma harboring a skipping mutation of mesenchymal‑epithelial transition exon 14: A case report.

Capmatinib is a medication used to treat patients with non-small cell lung cancer (NSCLC) who have a specific genetic mutation known as a mesenchymal-epithelial transition exon 14 skipping mutation. Previous clinical trials have reported that capmatinib treatment has a high objective response rate in patients with this genetic mutation. However, there have also been rare reports of patients developing interstitial lung disease (ILD) following capmatinib treatment, which can be life-threatening. The present case study reports the treatment of a patient who developed ILD after 6 weeks of capmatinib treatment for NSCLC, which was resolved following application of corticosteroids. The present case demonstrated that early recognition of the onset of ILD and discontinuation of capmatinib treatment, along with the prompt initiation of corticosteroid administration, can lead to complete resolution of ILD.

Lee BJ ，Chang CY 《-》