MET No. 14 outer appende jump mutant merged MET amplification patients, Savidi first -line treatment brings continuous benefits

*For medical professionals for reading reference

The treatment of Sevotinib first -line treatment has been effective, and it is an efficient and safe treatment option for patients with MET abnormalities.

This is a 69 -year -old female patient, which is diagnosed with the hypotomagic low -differentiated adenocarcinoma in the left lung leaf. MET No. 14 outer slogan jump mutation and MET amplification, the immunohistochemical result is PD-L1 negative. Patients have gradually improved their symptoms through the first -line treatment of Savininib, and the lesions have been significantly reduced. The recent review still maintains stability of the disease (SD). The case was provided by Professor Lin Jinpei from Fujian Cancer Hospital, and invited Professor Huang Zhengrong of Fujian Cancer Hospital to comment.

Resume

Basic situation: Patients, 69 years old, were admitted to the hospital for the "more pain in the left groin area in January" on November 12, 2021.

Previous history: level 3 (extremely high risk) for more than 10 years, with a maximum blood pressure of 180/100mmHg, and regularly taking Mitolol and chorusan potassium tablets to control blood pressure. The blood pressure fluctuations are in the normal range. Type 2 diabetes for more than 6 years, and the empty blood glucose is up to 13.3 mmol/L. It regularly takes two metformin and Akaba sugar for hypoglycemic treatment. The blood glucose fluctuates in the normal range. In the past, the "cervical and lumbar disc herniation" surgery was performed in 2010 and 2019.

Examination: ECOG scores are 3 points, Shenqing, wheelchair admitted to the hospital, the left stitch can touch a swollen and large lymph nodes, about 2.0cm × 2.0cm, hard and fixed, borders are clear, no obvious tenderness, L5 vertebral spine spines There are tenderness and tap pain.

Detection of Pulmonary Pingling on November 30, 2021: It is in line with infiltrating low -differentiated lung adenocarcinoma. IHC: CK20 (-), CK5/6 (-), CK7 (+), Ki67 (20%+), Napsina (+), P40 (-), P53 (80%+), TTF-1 (+).

Detective Pastation of pubic tissue on December 1, 2021: It is in line with the metastasis of lung adenocarcinoma. IHC: CK5/6 (-), CK7 (+), Ki67 (30%+), Napsina (+), P40 (-), TTF-1 (+), CDX2 (-), SATB2 (-), CK20 (CK20 -), P53 (20%+).

On December 17, 2021, the chest CT: left pulmonary tip occupation (3.5cm × 3.1cm). Considering the possibility of lung cancer, it is necessary to follow up with multiple lymph nodes (1.7cm × 1.1cm).

Pulmonary tissue gene test: MET No. 14 outer slogan jump mutation (86.4%of mutation abundance), MET amplification (copy number 9.4). IHC: PD-L1 negative, TPS 40%, CPS 45.

Diagnosis of admission: hyfolickness of the left lung lobe low -differentiated adenocarcinoma, left pulmonary, septum, perioprocytes around the pelvic foundation and left side groin lymph node metastasis, multiple bone transfers CT2AN2M1C IVB stage To.

The patient was diagnosed with left lung cancer merging multi-hair lymph node metastasis and multiple bone metastasis (CT2AN2M1C IVB stage). Genetic detection showed that there was MET No. 14 external appearance jump mutations and metaplasia, and the immunohistochemistry displayed PD-L1 negative. Patient's first -line treatment has adopted Savatinib and has been treated so far. Left lung cancer and multiple lymph nodes have been significantly retracted, and SDs have maintained the last review.

During the treatment period, the edema below the knee of the bilateral bilateral limbs was occurred. After diuretic and swelling, the edema quickly retreated. In addition, the patient has repeatedly discharged the stool one week after treatment. The hemoglobin is 59g/L. The patient stopped the discharge of the black stool through the hemostasis and blood transfusion, and the hemoglobin rose to 89g/L. Considering that the patients in this case have no symptoms of black stools in the past, and there is no history of intestinal ulcer -related medical history. After black stools, enteroscopy indicates that the colon ulcers are not in line with the current adverse reaction catalog in Savacinib, and more may require more. Clinical research data and further research are clear.

Provide experts

Professor Lin Jinpei: Met No. 14 outer appende jumping mutation and mutation combined with MET amplification patients, Saverninib achieves the effect and safety double harvest

The 69 -year -old female patient was diagnosed with non -small cell lung cancer (NSCLC) merged multi -hair lymph nodes metastasis and multi -bone metastasis. Due to the merger of MET jumping mutations and metamorphic amplification due to Met 14, the signs gradually improved. The signs gradually improved. From a wheelchair to walking; the lesion subsides, and the left groin can be touched by a swollen large lymph nodes before treatment. So far, patients have continued to benefit.

Met No. 14 outer Xianzi jump mutation detection has obtained a clear recommendation from many domestic and foreign guidelines. In the "Guidelines for Clinical Practice (2021)" [1] [1] [1] of non -small cell lung cancer molecular pathological test, MET14 outer sub -jump mutation is listed as a "compulsory gene". The "2022 Edition of the China Clinical Oncology Society (CSCO) NSCLC Diagnosis and Treatment Guide" [2] The test recommendation level of the MET14 outer Xianzi jump mutation has been increased from II -level recommendation in the 2021 guide to level I recommendation. It can be seen that the importance of clinical clinicality in MET14 is beyond doubt.

With the continuous research and development of MET inhibitors such as Savininib, the prognosis of patients with NSCLC patients in MET14 has improved. This case is MET14 outer Xianzi jumping and mutation with MET amplification, and the treatment is more tricky. A number of studies have confirmed the curative effects of Savidini in different cancer species in different cancer species in different cancer species in Met14. Phase II registered research [3] In total, 70 patients with jumping and mutations in Met14 outer14 or patients with jump mutations (PSC) or other NSCLC subtypes received Savacinib for treatment. The results showed that the objective relief rate ( Orr) is 49.2%, and the disease control rate (DCR) is 93.4%. In 2022, the European Lung Cancer Conference (ELCC) updated the results of the final total survival (OS) results and Asian group analysis results of the Savernini registered research [4]. The median OS of the patient is 19.4 months, and the median OS patients with brain metastases are 17.7 months. Whether it is a crowd or the Asian group, Savigi has a good effect. Moreover, Savacinib has good safety and tolerance, and the treatment related adverse reactions are mostly 1-2. In TATTON Studies [5], for NSCLC patients with MET amplification, Savidinib showed good and lasting anti -tumor activity.

In general, the efficacy and safety of Savotininib for the treatment of MET14 outer14 and the MET amplification patients have good efficacy and good safety, and have broad application prospects.

Expert Reviews

Professor Huang Zhengrong: Saverninib can bring a turnaround for the MET abnormal NSCLC merged and multiple metastasis patients

The patients in this case are diagnosed with NSCLC combined with the transfer of the left pulmonable, the hypertrophy, the lymph nodes around the pelvic foundation and the left side of the groin, and the bone is often metastasized. In June 2021, Savacini was listed in China and was approved to treat local advanced or transferring NSCLC for local jumping and mutations in the existence of MET14. In this case, patients with MET No. 14 outer appende jump mutation and mutations combined with MET amplification. Before the treatment of Savidinib, the L5 vertebral spinal spiny had tenderness and soreness; pain. Sevotinib shows the good efficacy of the primary lesion and the metastatic stove. The ECOG score is reduced from 3 to 2 points, which improves the quality of life of patients.

In NSCLC, the abnormal activation of C-MET protein can occur through multiple mechanisms. Generally, there are several ways to express the expression of C-MET protein; MET genes amplification, mutation, and metal gene fusion. The incidence of MET genes amplification in lung adenocarcinoma is about 2 % to 4 %, and it rarely coexist with MET gene mutations [6]. In this case, the patient's existence of MET No. 14 out -of -revealing jump mutations and MET amplification. TATTON Studies [5], orchard Studies [7] have confirmed the preliminary efficacy of MET enlarged patients after the treatment of EGFR-TKI resistance for EGFR-TKI, and verified the effectiveness of Savetinib for MET amplification in clinical practice. sex.

Savacini has significant clinical benefits to patients with NSCLC and MET amplification of NSCLC and MET amplification. Its listing brings opportunities to extend survival for such patients. Looking forward to the widespread application of Saverninib in the clinical practice of real world in the future, to help more MET abnormal NSCLC patients get better clinical efficacy and survival benefits.

Comment expert introduction

Professor Huang Zhengrong

Doctor of Medicine, Deputy Chief Physician

Director of Traditional Chinese and Western Medicine, Fujian Cancer Hospital

Member of the Expert Committee of the Chinese and Western Medicine Integrated Medicine Branch of the Chinese and Western Medicine Association

Member of the Tumor Rehabilitation Branch of Chinese Elderly and Senior Medical Society

Member of the Professional Committee of Cancer Drug Research of China Chinese Medicine Association

Member of the Taiwan Strait Medical Development Committee of the Medical and Health Exchange Association Cross -Strait

Deputy Chairman of the Cancer Rehabilitation Professional Committee of Fujian Province

Executive Member of the Professional Committee of Traditional Chinese and Western Medicine Integrated Cancer Integrated Cancer Association of Fujian Province

Member of the Cancer Medicine Branch of the Integrated Society of Traditional Chinese and Western Medicine in Fujian Province

Member of the Tumor Branch of the Fujian Society of Traditional Chinese Medicine

Introduction to experts

Professor Lin Jinpei

Fudan University Traditional Chinese and Western Medicine Combination Clinical PhDs

The attending physician of the Traditional Chinese and Western Medicine Integrated Department of Cancer Hospital in Fujian Province

Youth Committee of the first Chinese and Western Medicine Integrated Cancer Professional Committee of the Fujian Anti -Cancer Association

Secretary of the Cancer Pain Team of the Third Committee of the Pain Medical Branch of the Fujian Medical Association

Director of the Green Treatment Branch of the Fujian Straits Medical Health Exchange Association

references:

[1] Chinese Medical Society Pathology Branch, National Pathological Quality Control Center, Lung Cancer Group of the Chinese Medical Society on Cancer Branch, etc., etc. , 2021,50 (4): 323-332.

[2] China Clinical Oncology Society (CSCO) non -small cell lung cancer diagnosis and treatment guide 2022

[3] Lu S, Fang J, Li X, et al. Once-daily savolitinib in Chinese patients with pulmonary sarcomatoid carcinomas and other non-small-cell lung cancers harbouring MET exon 14 skipping alterations: a multicentre, single-arm, open -label, Phase 2 Study [J]. Lancet Respir Med. 2021; 9 (10): 1154-1164. [4] Lu s et al. (2022) Final OS Results and Subgroup Analysis of Savolitinib in Patients with Met Exon 14 14 SKIPPING MUTATATIONS (METEX14+) NSCLC.ELCC 2022,2MO.

[5] Lecia V Sequist, Ji-Youn Han, et al. Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: interim results from a multicentre , Open-Label, Phase 1B Study [J]. Lancet Oncol. 2020; 21 (3): 373-386.

[6] Zhao Bochen, the research progress of Lu Dan.c-met in lung cancer [J]. Modern oncology medicine, 2022,30 (1): 174-178.

[7] Sequist L V, Han J Y, Ahn M J, et al. Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: interim results from a multicentre , Open-Label, Phase 1B Study [J]. The Lancet Oncology, 2020, 21 (3): 373-386.

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