Professor Gongyou Ling: Savetinib's real world has great effects, win more benefits for patients with MET abnormalities

*For medical professionals for reading reference

In June, MET excellent cases are essence ~

As the high-selective MET-TKI Savininib was listed in China, it opened a new era of MET targeted therapy in my country. In order to improve the clinic doctor's understanding of MET pathways and promote the standardized diagnosis and treatment of rare mutant tumors, the medical media media specially launched the "MET victory in Wo -rare mutant tumor MET inhibitors for the treatment of excellent case collection activities".

In June, a total of 5 excellent cases were selected and published on the medical circles of the tumor channel. Provincial Hospital) Professor Zhang Junqiang, Professor Wang Jian of Jiangsu Provincial People's Hospital, and Professor Li Peng, Tianjin Medical University Cancer Hospital. In this regard, the "medical community" specially invited Professor Gong Youling of Huaxi Hospital of Sichuan University to summarize and comment on these cases to learn from clinical experience and promote the standardized diagnosis and treatment of MET.

Review of wonderful content

Patients with right lung adenocarcinoma (CT2N0M1 IVA) patients at the age of 1:75, after gene detecting MET14 out -of -MET14 jumping and mutation, the patient participated in the clinical trials of the Savinininini II phase II due to the patient's impact resistance. The best effect of the first -line treatment of Saivinib 600mg QD PO is the stability of the disease (SD) that has been narrowed (SD), and there is no progressive survival (PFS) for 22 months. (Click to view the full case)

Cases 2:71 years old MET14 have a left lung adenocarcinoma patient who jumps and mutations, and is in a period of acute aggravation of chronic obstructive pulmonary disease. After the Saivotinib 600 mg QD PO new assisted treatment, the tumor reached most of the relief (PR), and the treatment process was smooth. The patient had no drug -related adverse reactions. After that, the patient was successfully removed and recovered well after surgery. (Click to view the full case)

Case 3:49 years old MET14 outer outer appende jumping and mutation IIIA stage left pulmonary adenocarcinoma patients, discussed with multidisciplinary diagnosis and treatment (MDT), and discussed with patients and their families, gave Savidi 600mg QD PO neooth treatment. Essence After 21 days, the efficacy assessment found that the tumor has shrunk significantly and reached PR, creating better conditions for subsequent surgery. (Click to view the full case)

Cases 4:64 years old Patients with IVB pulmonary adenocarcinoma have previously intended to use Arotinib combined with chemotherapy, but patients have suffering from breathing difficulties after using Arotinib, and they cannot tolerate chemotherapy. The number of patients in the second -generation sequencing (NGS) of the patient increases the number of copies of the MET gene, and the fluorescent in situ hybrid (FISH) test is further verified as the local amplification. Subsequently, the patient switched to the MET inhibitors Savatinib. After the treatment, it quickly took effect. The bone pain was significantly alleviated compared with the front. The difficulty of breathing was significantly relieved. Since the follow -up, the case has been used for more than July, and it has continued to benefit. (Click to view the full case)

Case 5:55 years old EGFR 21 ostelopence L858R (21L858R) mutant for right pulmonary gland squama carcinoma is accompanied by multi -hair lymphoma metastasis (T1CN3M0IIB stage) patients. Bit), so left leaf lobe resection. After surgery, the genetic test of the patient showed that the EGFR 21L858R mutation and MET amplification were displayed. According to the consultation opinion, the patient continued to use Oshitinib after surgery, but the brain metastase reclosure again. After that, the patient switched to the treatment of the wave knife and the two targets of Oshitinib+Savatinib. After 2 months, the brain metastases disappeared, and the upper lung massage and the right lower neck were narrowed. At present, patients have obtained an unprepared survival period (PFS) for about one year, and they are still undergoing benefits. (Click to view the full case)

Professor Gong Youling summarized the comment

In June 2021, my country ushered in the first high -selective MET inhibitor Savinib, which brought accurate targeted treatment for patients with abnormal MET pathways. With the widespread clinical application of Savacinib and continuously summing up medication experience, it is essential for guiding clinical practice and standardizing diagnosis and treatment.

In June 2022, a total of 5 excellent cases were released in the "MET Winning Case in Wo" project, covering a variety of MET pathways, including MET14 outer Xianzi jump mutations, primary MET amplification, and secondary MET amplification. And it is worth mentioning that there are two cases of Savetinininin therapy this month, which provides important reference significance for patients with Savidinib to improve surgical effects and improve prognosis for patients with early and mid -term NSCLC.

1

Precision treatment, test first

As MET-TKI is approved in my country, clinical workers should also strengthen the attention of MET pathways in daily work and master the methods of precise testing to provide guidance for subsequent precision treatment.

The 2022 Edition of the China Clinical Oncology Society (CSCO) NSCLC diagnosis and treatment guidelines [1] recommended, and the test of non -scale carcinoma tissue stages and stage IV patients in stage III and stage IV. Essence

At present, the detection method of exposure and mutation of MET14 in clinical practice is mainly to reverse the transcription-polymerase chain reaction (RT-PCR) and NGS (including RNA-NGS and DNA-NGS). Different detection methods have their own advantages and disadvantages, such as high accuracy of RT-PCR and fast detection speed, but high quality requirements for gene fragments; RNA-NGS also has the characteristics of high accuracy and high sensitivity, and can detect different ones at a time. Mutation type, but because RNA is easy to degrade and affects the test results, quality control should be done before testing; DNA-NGS is widely used in clinical application, but the coverage of MET gene probable probe may cause leakage-based test-based testing. [2]. Therefore, clinicians should choose the appropriate detection method according to the specific situation of the patient. MET amplification includes primary amplification and secondary/co -drive amplification. Its form includes two types, namely local amplification and chromosomes. FISH is the standard method for detecting MET amplification, which can distinguish local amplification and multi -body. At present, the judgment standard for FISH test MET amplification has not yet reached a consensus. Some studies believe that the MET gene copy number (CNG) ≥5, and the MET/CEP7 ratio ≥2.0 can be defined as local amplification, CNG ≥ 5 but MET/CEP7 The ratio <2 is defined as MET multi -body [3]. NGS can also be used to detect MET amplification, but it may miss MET versatile, and whether the increase in MET copies detected by NGS is equivalent to the classic amplification in the classic sense.

The above -mentioned case 4 is a patient with an amplification of the original MET. After the NGS detection prompts MET gene copy number increases, the FISH test is used to further verify the local amplification of MET. The importance of precision detection.

2

From MET14 outer exposure jump to MET amplification, the efficacy and security advantages of Savidib highlight

Based on the positive results obtained in Phase II clinical research, Savininib has been approved by NSCLC, which is approved by Met14 outer jumping mutation. Data [4,5] shows that among the overall crowd, the median total survival (OS) treated in Savidinib for 12.5 months, the median PFS is 6.9 months, and the objective relief rate (ORR) is 49.2%. The disease control rate (DCR) was 93.4%, and it was safe and good. It also showed significant survival benefits in sub -groups such as lung sarcoma -like cancer, menstrual treatment, and brain metastases.

The above -mentioned cases 1, 2, and 3 are patients with jumping and mutations from MET14, and Savidi therapy has achieved significant effects. Especially in case 1, patients have obtained a 22 -month PFS, far exceeding historical data, which fully reflects the long -term survival advantage of Savidi.

Moreover, for patients with extension of primary and secondary metas, Savidi also has a good effect. Secondary MET amplification is an important mechanism for EGFR-TKI to treat drug resistance. TATton Study [6] shows that for patients with first/second-generation EGFR-TKI patients, whether there is a T790M mutation, Savidi+Osh Dear Niger has a good and lasting anti-tumor activity. The ORR is 64%-67%, and the median PFS is about 10 months. As for the lack of standard treatment schemes to receive multi -line therapy Ostininib with the MET amplification, Savidi+Oshitinib can still bring 30%ORR and 5.4 months of median PFS.

For patients with amplification of primary MET, the current clinical treatment experience has limited experience. Among the above case 4, patients with extended primary MET use Saverninib to treat rapid effects. The symptoms of bone pain and dyspnea are significantly relieved. Patients can take care of their own life. They can be discharged in just 5 days. The remaining PFS. Its treatment process suggests that the use of Savidoni targeting treatment may bring greater benefits to patients with amplification, and it has important reference significance for the treatment of such patients in clinical practice.

3

Savininib neo -assisted therapy for tumor reheating has a significant effect, helping improve the effect of surgery

In order to increase the complete resection rate of NSCLC tumors, reduce the transfer of tumors from distant metastasis and extend the survival of patients, the application of neo -assisted targeted therapy to patients with surgery has become a research hotspot in recent years. Research (such as the Neos Study of Oshitinib newly assisted targeted therapy) showed that new assisted targeted therapy can reduce tumors, achieve tumor downside, thereby reducing surgery Risk of recurrence.

For MET new -assisted targeted therapy, although there is still lack of random control research data, many cases have been reported to provide a reference for clinical practice. Among the above cases, the tumors have been significantly reduced after the treatment of Saverninib newly auxiliary treatment, and basically achieved PR, creating opportunities for subsequent improvement of surgical efficacy. Moreover, the safety of the new assisted therapy for Savacii has not affected the implementation of subsequent surgery, and the risk of perioperative complications has not been increased, which further confirms the clinical value of Savidinib neo -assisted therapy.

With the accumulation of more clinical clinical cases of Saverninib neo -auxiliary treatment cases, I hope to summarize experience from it and provide reference for guiding clinical treatment. At the same time, I hope to carry out research in the future to further consolidate the benefits of Saivininib neo -assisted therapy.

All in all, as the first high -selective MET inhibitor in China, Saverninib has been widely used clinically in China for one year in China. Multi -patient seeing the dawn of long -term survival, pushing the precision diagnosis and treatment of lung cancer has entered a new journey. In the future, I hope to further standardize the diagnosis and treatment of rare targets to mutate lung cancer, so that patients will benefit from accurate diagnosis and treatment to the greatest extent. Expert Introduction

Gong Youling

Deputy director

Chief Physician Master Graduate Tutor

Visiting scholars in South Carolina, USA

Member of the International Ling Cancer Society

Executive Member of the Special Medicine Branch of the Chinese Society of Toxicology

Member of the Tumor MDT Special Committee of the Chinese Physician Association

Member of the Radible and Treatment Committee of the Chinese Medical Association

Standing Committee of the Sichuan Medical Association Radiation Tumor Special Committee

Deputy Chairman of the Sichuan Provincial Medical Promotion Council Tumor MDT Special Committee

Director of the Sichuan Cancer Society and Standing Committee of the Professional Committee of the Lung -Cancer

Editorial Committee of "Chinese Cancer Magazine"

references:

[1] 2022 Edition of the China Clinical Oncology Society (CSCO) non -small cell lung cancer diagnosis and treatment guide.

[2] Non-small cell lung cancer molecular pathological test clinical practice guide (2021 version) [J]. Chinese pathology magazine, 2021,50 (4): 323-332.

[3]Lai GGY,Lim TH,Lim J,et al.Clonal MET Amplification as a Determinant of Tyrosine Kinase Inhibitor Resistance in Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer.J Clin Oncol.2019 Apr 10;37 (11): 876-884.

[4]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.

[5] Lu s et al. (2022) Final OS Results and Subgroup Analysis of Savolitinib in Patients with Met Exon 14 Skipping Mutations (Metex14+) NSCLCCCC 2022,2mo.

[6]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.

*This article is only used to provide scientific information to medical people, and does not represent the viewpoint of this platform

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