What should be done in colorectal cancer patients with MET amplification?

*For medical professionals only for reference This patient is a 49-year-old male colorectal cancer (CRC) patient.
During the previous chemotherapy, the tumor markers improved only slightly, and the tolerability was not good.
He developed repeated intestinal obstruction and abnormal liver function.
Therefore, the treatment was interrupted and no antitumor therapy was given during the period.

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On October 18, 2021, the patient was readmitted to the hospital.
The results of genetic testing showed that the patient had a MET gene mutation, and the mutation type was amplification mutation
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Since the patient himself resisted chemotherapy and had the willingness to target therapy, the patient began to receive sevolitinib targeted therapy from October 19, 2021
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On December 6, the curative effect evaluation was partial remission (PR), and the tumor regression rate was over 40%
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The patient's progression-free survival (PFS) to date is 6 months, and the patient is still in PR status
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This case was provided by Professor Wang Xiaojie of Fujian Cancer Hospital and invited Professor Guo Zengqing of Fujian Cancer Hospital to comment
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Case profile Basic information Patient information: Deng Mou, male, 49 years old
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Past and family history: None special
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Liver MRI: Consider transverse colon cancer with multiple metastases to liver, abdominal cavity and retroperitoneal lymph nodes
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PET-CT: The wall of the ascending colon near the hepatic convoluted tube is thickened and has high metabolism.
Considering that the tumor still has high activity; there are multiple lymph nodes in the left clavicle area, mediastinum, medial crus of the right diaphragm, abdominal cavity, retroperitoneum, and left iliac vessels Enlarged, high metabolism, tumor metastasis is considered; multiple liver masses, high metabolism, tumor metastasis is considered; small nodules in the periintestinal fat space with cord-like shadows, left femoral tube nodules and vesicorectal fossa nodules have high metabolism, and pelvic cavity If there is a small amount of effusion, tumor implantation and metastasis should be considered; there are multiple small nodules in both lungs, and the metabolism is low, so close follow-up is recommended
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Next-generation sequencing (NGS): The targeted drug-related gene detection is KRAS gene mutation, and the mutation type is amplification mutation; other systemic mutations are detected as MET gene mutation, and the mutation type is amplification mutation
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Microsatellite instability (MSI) and mismatch repair (MMR) gene detection: MSI detection results indicate MSI-L/MSS; MMR gene detection results indicate that the pathogenicity of DNA mismatch repair-related genes was not detected in this sample mutation
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Diagnosis: Colon hepatic flexure adenocarcinoma with multiple metastases in the retroperitoneum, mediastinum, left clavicle and other lymph nodes, liver, abdominal and pelvic cavity (cT4aN+M1, stage IV)
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Table 1.
Efficacy evaluation of patients during treatmentFig.
1 CT examination results during patient treatment Common cause of tumor-related death
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Benefiting from the continuous development of precision medicine and the continuous progress of genetic testing technology, the clinical diagnosis and treatment of CRC patients has undergone tremendous changes.
Clarifying the type of gene mutation to receive corresponding targeted therapy is expected to bring greater clinical benefits to CRC patients [1] ]
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Studies have shown that mesenchymal epithelial transforming factor (c-MET) is a cell surface receptor of tyrosine kinase activated by hepatocyte growth factor (HGF)
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Activation of the c-MET/HGF signaling pathway regulates multiple biological processes, including cell motility, cell proliferation, angiogenesis, epithelial-mesenchymal transition, and cancer cell development and progression
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Recent studies have shown that the c-MET/HGF signaling pathway is involved in the carcinogenesis of CRC
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Given that MET plays a key role in cancer progression, inhibition of MET may bring clinical benefits to the treatment of patients with solid cancers with abnormal MET pathways [1,2]
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The patient did not initially undergo genetic testing, and only received bevacizumab combined with chemotherapy.
Later, due to poor improvement of tumor markers and poor regression of liver lesions, treatment was discontinued
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After being readmitted to the hospital, the result of genetic testing was MET amplification.
Due to the strong resistance of the patient to chemotherapy and the willingness to receive targeted therapy, the patient finally received the MET inhibitor sivotinib.
During the follow-up, the short-term effect of PR was obtained.
At the latest follow-up, the tumor remission was further deepened, and it is currently in continuous benefit
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It can be seen that the timely identification of mutated genotypes and the selection of appropriate targeted drugs can maximize the clinical benefits of CRC patients
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Fortunately, the patient underwent genetic testing in a timely manner under the condition of poor initial treatment effect, and it was confirmed that he received sevolitinib treatment in a timely manner after MET amplification, and finally achieved PR, and the subsequent tumor remission was further deepened
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Therefore, genetic testing should be performed in CRC patients before clinical treatment.
For CRC patients with MET amplification, MET-TKIs with excellent efficacy and safety (such as civotinib) should be selected to prolong the treatment time and improve the patient survival
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Expert Comments on Prof.
Zengqing Guo: Second-line treatment of sevolitinib in CRC patients with MET amplification can lead to rapid tumor PR Phosphorylation can significantly inhibit the proliferation of tumor cells with abnormal MET pathway[1]
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A dose-finding phase I trial explored the therapeutic potential of sevolitinib in patients with gastrointestinal tumors.
The exploratory analysis included 14 patients, including 4 patients with MET 3+, all patients with gastric cancer (GC); 2 patients were MET 2+, including 1 GC and 1 rectal cancer (RC); 4 patients were MET 1+, including 1 GC, 1 RC, and 2 melanoma; 4 patients MET0 patients, including 2 melanomas, 1 GC, and 1 sarcoma
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Two of the four patients with MET 3+ had MET amplification confirmed by FISH
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Notably, one GC patient (B6-0044) with MET overexpression (3+) and amplification (MET/CEP7 ratio, 7.
3) achieved a durable PR of 297 days, and another MET-amplified GC patient (MET/CEP7 ratio, 7.
6, B6-003) achieved 86 days of disease stabilization
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This study suggests that for patients with gastrointestinal tumors with MET amplification, savatinib can bring certain efficacy, or can be used as a potential treatment strategy
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The patient achieved tumor PR at follow-up more than 1 month after receiving sivotinib targeted therapy.
The latest follow-up showed that the degree of remission was further deepened.
So far, the patient is still in continuous benefit, which re-validates sivotinib therapeutic benefit
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At present, sivotinib has shown potential therapeutic potential in a variety of tumors, and the research of sivotinib in the clinical treatment of CRC is also actively progressing [1,3]
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It is believed that with the continuous in-depth development of clinical research, savotinib is expected to bring greater clinical benefits to patients with MET-amplified CRC
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Case Review Expert Profile Professor Guo Zengqing Executive Director of Tumor Cadre Ward (Ward 20) (Ward 19) of Fujian Cancer Hospital Executive Director of Clinical Nutrition Department and Deputy Director of Cancer Bioimmunotherapy Center Deputy Director of Fujian Provincial Cancer Immunotherapy Quality Control Center Deputy Director of Fujian Provincial Clinical Nutrition Therapy Quality Control Center Member of the Standing Committee of the Cancer Nutrition Professional Committee of the China Anti-Cancer Association Member of the Cancer Targeted Therapy Professional Committee of the China Anti-Cancer Association Member of the Standing Committee of the Biliary Tumor Professional Committee of the Chinese Society of Clinical Oncology (CSCO) Chinese Society of Clinical Oncology (CSCO) Member of the Tumor Nutrition Expert Committee Member of the Colorectal Cancer Professional Committee of the Southern China Cancer Clinical Research Association Chairman of the Tumor Nutrition and Supportive Therapy Professional Committee of the Fujian Anti-Cancer Association Standing member of the Professional Committee of Medical Oncology, Fujian Provincial Anti-Cancer Association, Standing Member of the Professional Committee of Gastric Cancer, Fujian Provincial Anti-Cancer Association, Deputy Director of the Professional Committee of Clinical Nutrition, Fujian Provincial Nutrition Society Chief Physician, Medical Oncology Special Needs Ward/Clinical Nutrition Department Member of the Second Professional Committee of Cancer Rehabilitation and Palliative Care of Fujian Anti-Cancer Association Member of the First Professional Committee of Oncology of Fujian Anti-Cancer Association Member of the Digestive System of Fujian Association of Integrative Medicine Member of the 4th Committee of the Diseases Society Member of the Nutrition Science Group of the Cancer Nutrition Professional Committee of the Chinese Anti-Cancer Association Specializing in the diagnosis and treatment of malignant tumors of the digestive tract, good at the treatment of malignant tumors with malnutrition and coagulation disorders References: [1].
Seyed Mostafa Parizadeh et al.
The Potential Therapeutic and Prognostic Impacts of the c-MET/HGF Signaling Pathway in Colorectal Cancer.
IUBMB Life.
2019 Jul;71(7):802-811.
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[2].
Seung Tae Kim et al.
Combination of Docetaxel Plus Savolitinib in Refractory Cancer Patients: A Report on Phase I Trial.
Transl Oncol.
2019 Apr;12(4):597-601[3].
https://clinicaltrials.
gov/ct2/results?cond=CRC&term=Savolitinib&cntry=&state=&city=&dist=.
*This article is only for providing scientific information to medical professionals and does not represent the views of this platform