Professor Li Juan: How can patients with MET abnormal live alive?6 typical cases tell you

*For medical professionals for reading reference

In July, MET excellent cases are essence ~

With the listing of the first high -selective MET inhibitors, the first year of the MET in China, the patients with abnormal MET pathways have gone out of the predicament of the previous "medicineless". 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 July, a total of 6 excellent cases were selected and published on the medical circles of the tumor channel. Professor Chen Shijie, Fujian Cancer Hospital, Professor Tang Jincong, Ningbo Huamei Hospital of the Chinese Academy of Sciences, and Professor Wang Lei, Dalian Friendship Hospital. In this regard, Professor Li Juan, a Sichuan Cancer Hospital in Sichuan Province, summarized and commented on these cases to learn from clinical experience and promote the standardized diagnosis and treatment of MET.

Review of wonderful content

Case 1

65-year-old left pulmonary adenocarcinoma with patients with multiple metastasis (CT4N3M1 IVB) patients in the septum and left pulmonary lymph nodes, brain, and whole body, PD-L1 high expression, first-line therapy adds PD-1 antibody combined with CTLA-4 dual anti-United Ao The clinical study of Tetinib has brain metastases 3 months later. Because the patient exists with MET14 outer appearance and jumping and mutations, the second -tier therapy chooses Savarini targeting therapy, and the efficacy assessment is partially alleviated (PR). Yu is still in the continuous benefit. (Click to view the full case)

Case 2

A 63 -year -old male patient, the first diagnosis of right lung adenocarcinoma with negative gene is accompanied by the right bronchial lymph node metastasis, the right lung metastases, pleural metastasis, and the left lung grinding glass stove (malignant) (CT4N1M1B, IV). Patients have received the first -line treatment of Pemeter+Card Platinum+Bevarzab, Geffitinib+Bevarzab maintains the treatment, and replaced it with Oshitinib+Bevar beads after the disease progress (PD) Single anti -anti -second -line treatment. After 4 months of treatment, the lung residial lesions were abolished, and the lung puncture biopsy testament was performed before surgery. The tissue genetic testing reminded the patients to mutchay the EGFR No. 21 outer appendage L858R and Met 14 outer appende. Patient's third -line treatment was treated with Savidib+Oshitinib. So far, PFS is more than 9 months and is still under treatment. (Click to view the full case)

Case 3

74 -year -old female patients, postoperative diagnosis as MET14 out -of -the -lobe -like lobe sarcoma -like cancer (PT4N0M0 IIIA stage), which is diagnosed with jumping mutations, and has a pulmonary grinding glass nodule (GGO of the lower lobe inner base section of the left lung lemmer (GGO ) GGO of the back of the right lung. Patients underwent auxiliary chemotherapy after surgery, but the curative effect was not good. In just 4 months, adrenal metastases occurred. Subsequently, the patient was treated with oral cipotinib. After 4 months, the review showed that the adrenal metastases were reduced, but the patient had brain metastases after 8 months. Considering that patients may have tumor resistance, they are treated for patients for treatment. After nine months of medication, the review showed that the brain metastases were reduced, and the patients have reached 15 months of PFS so far, and they continue to benefit. (Click to view the full case)

Case 4

The 50 -year -old male patient was first diagnosed with EGFR 19DEL mutant left lung adenocarcinoma with left pulmonary, septum, bilateral collarbone area, and post -peritoneal lymph node metastasis (CT3N3M1B IVA stage). +Chemotherapy+antiovascular generation treatment and immune+chemotherapy. After the three -line treatment resistance, genetic detection shows the EGFR 19DEL mutation, while the immunohistochemical (IHC) test found that MET is expressed. After that, the patient received a combination of glycin and albumin, but all of them were quickly PD. After the tumor was treated with Oshitinib+Savinininib six -line treatment, the tumor was PR. (Click to view the full case)

Case 5

The 55 -year -old male primary MET enlarged small intestine malignant tumor is accompanied by multiple metastatic patients, and has successively used chemotherapy and immune combined chemotherapy, but the results are not good, and PDs soon occur. Considering the existence of MET amplification, it is replaced by the Savininib (600mg QD) combined with Kapibide. After the treatment, the patient's primary lesions and liver and adrenal glands have gradually narrowed. During the recent follow -up, some lymph nodes in the peritoneal area of ​​the full abdomen were re -found that the lymph nodes in the peritoneal area increased before. At present, the patient has used the Savininib plan for more than August and continues to benefit. (Click to view the full case)

Case 6

A 64 -year -old male patient, diagnosed with primary MET's amplified right lung adenocarcinoma with neck lymph nodes, collarbone lymph nodes, peritoneal multiple lymph nodes, right adrenal glands and multiple bone metastases (CT1CN3M1C IVB period), and in the United Beduzumab joint combination After the first -line treatment of platinum dual drug chemotherapy, liver metastases occur. After that, patients were used in foreign hospitals and chemotherapy and other scheme chemotherapy, but the effect was not satisfactory. After the treatment of the four -line treatment of Savaci, the patient's bone pain improved. After 2 months, the efficacy was evaluated as PR, and it has received about 6 months of PFS. (Click to view the full case)

Professor Li Juan summarized the comment

In June 2021, my country's first high -selective MET inhibitor Savinib was approved to go public, opening a new era of MET targeted therapy in my country. Since the first anniversary of listing, Saverninib has been widely used in the treatment of abnormal MET pathways in clinical practice, which has brought hope of long -term survival to a large number of patients. At the same time, improving the concept of MET diagnosis and treatment of clinicians, promoting the standardized use of Savacibinib, so that patients with abnormal MET pathways can benefit to the greatest extent, which is more important clinically. In July 2022, a total of 6 excellent cases were released in the "MET victory in Wo" project. In addition to MET14, the jump jumping and jumping and mutation, as well as the expressions of the original MET amplification and IHC detection. These different MET pathways Abnormal patients have significantly benefited from the treatment of Savacinib. In terms of cancer species, in addition to common lung adenocarcinoma this month, it also includes pulmonary sarcoma -like cancer (PSC) with poor prognosis and small intestine malignant tumors. These cases are very representative and have practical guiding significance for clinical treatment.

MET14 outer appende jumps and mutations, real world cases continue

In the II Studies of PSC or other NSCLC patients used in Saverninib for MET14 or other NSCLC patients [1], the median PFS treated by Savidi is 6.9 months, and the median total survival period (OS) reaches it. 12.5 months, and it has shown good anti -tumor activity to difficulty governance people such as elderly, poor baseline conditions, PSC and brain metastases. In addition, Savacinib is good at safety and has not observed interbctoral lung disease.

Since its listing, Savaci has also performed well in clinical practice. The above cases 1-3 are patients with lung cancer patients who have jumping and mutations from MET14. Among them, all cases 1 and case 3 have brain metastases. Case 1 receives immunotherapy before, but the effect is not good. The lung lesions and brain metastases are significantly reduced after the treatment of Savininib. Patients first were treated with clipininib first, but brain metastases occurred a few months later. After switching to Savininib, the brain metastases were reduced. So far, PFS, which has been achieved for 15 months, far exceeds that of such patients. Historical data for treatment. It can be seen that for patients with less brain metastases in the treatment, Savidi provides an efficient treatment option. Moreover, the treatment process of Case 3 also tells us that patients with Cizyininini resistance are feasible to use Savininib.

Case 2 is the rare EGFR mutation combined with MET No. 14 outer sub -jump mutations in the clinical clinical. After three -month PFS for more than 9 months after the three -line treatment of Savininib+Oshitinib. The treatment process shows that for the EGFR/MET dual -drive, double target precision treatment has considerable anti -tumor activity.

MET amplification, Saverninib is expected to bring better long -term benefits to patients with different cancers

MET genes can be used as a primary drive gene or a secondary/common drive gene. At present, the treatment of the original MET is limited. Research [2,3] showing that ACSE TRIAL, Geometry Mono-1, etc. show that for the primary MET amplification or excessive expression groups, the effect of MET-TKI single drug treatment is limited, even among highly amplified crowds. Therefore, the primary MET amplification still needs to explore better treatment solutions.

The above cases 5 and case 6 are patients with the primary MET amplifying small intestine malignant tumors and right lung adenocarcinoma, and there are multiple metastasis. Savacinib showed a good effect during the treatment. Patient's treatment provides a certain reference significance. In the future, we also look forward to more and better treatment plans to benefit patients with extension of primary MET.

At the same time, these two cases also remind clinicians that patients with Savidi in different cancers have good treatment prospects. In the pre -clinical study [4] in the 2015 Sevotinib, Saverninib showed a good anti -tumor activity in gastric cancer -derived tumor -transplanted models, indicating that it has the potential for treatment of MET amplification gastric cancer. In Viktory [5] in Phase IIII, the ORR for patients with gastric cancer receiving Savidoni drugs for gastric cancer was 50%. At present, the research of many Savacinib for other MET pathways is underway, let us wait and see.

After EGFR-TKI is resistant, MET is expressed, and the effect of dual target treatment is considerable

The incidence of MET expressed in the overall NSCLC patients is 25%-75%, which is one of the important mechanisms for EGFR-TKI to resist [6]. The above-mentioned case 4 was initially diagnosed with EGFR 19DEL mutations. The left lung adenocarcinoma was metastasized by the three generations of EGFR-TKI targeted therapy, immune+chemotherapy+anti-vascular generating therapy and immune+chemotherapy. After the PD again, in order to clarify the drug tolerance mechanism, the patient's lung puncture biopsy, the IHC test shows that MET excessive expression (95%strong+), at the same time, the genetic test shows that the patient still has the EGFR 19DEL mutation. After that, the patient tried to use the two different chemotherapy schemes, combining Duocisai and albumin, but it was soon PD again, suggesting that chemotherapy may have poor treatment for EGFR mutations and MET's excessive expression.

After the treatment of the two targets of Savininib+Oshitinib, the tumor was significantly reduced after 21 days after the review was significantly reduced to PR, and the patient received a total of 5.6 months of PFS. The treatment process of this case suggests that patients with IHC detection of MET may benefit from MET targeted therapy, and in clinical practice or it is necessary to perform IHC detection MET in patients with lung cancer. Moreover, in an exploration analysis of TATTON research [7], the objective relief rate (ORR) and disease control rate (DCR) of patients with IHC positive (IHC50+) see the efficacy signal. In addition, Savannah Studies [8] will be announced for the first time on the World Ling Cancer Conference (WCLC) in 2022. After the first Oshitininin resistance is announced, the MET expression group will be treated with the treatment data for the treatment of data from Oshitininib. From the data published in the study summary, 300mg QD+Oshitinib 80mg QD group data can be seen that the ORR of FISH 5+ and/or IHC 50+ patients is 32%, and the duration of the median relief (DOR) is 8.3 to 8.3 For a month, the mid -position PFS is 5.3 months; the ORR of FISH 10+ and/or IHC 90+ patients is 49%, the median DOR is 9.3 months, and the mid -bit PFS is 7.1 months; no FISH 10+ and/or or/or or or or/or or/or or/or or/or or/or/or/or there The ORR of IHC 90+ patients is 9%, the median Dor is 6.9 months, and the mid -position PFS is 2.8 months. The result shows that for patients with higher expression levels, Savacinib combined with Oshitinib dual target combination treatment effect is more significant. Let us look forward to more disclosure of data.

Expert Introduction

Professor Li Juan

Doctor of Oncology, Deputy Chief Physician, Master Graduate Tutor

Director of the Second Hospital of the Department of chest oncology hospital in Sichuan Province

Visiting scholar at the American Meo Clinic

Member of the China Anti -Cancer Association Tumor Transfer Special Committee

Youth Member of the China Anti -Cancer Association Lung Cancer Special Committee

Vice President

Deputy Chairman of the Sichuan Anti -Cancer Association Senior Tumor Treatment Special Committee

Executive Member of the Sichuan Anti -Cancer Association Lung Cancer Special Committee

Executive Member of the Sichuan Medical Association Evidence -based Medical Committee

Executive Member of the Sichuan Medical Promotional Association Oncology MDT Special Committee

"China Ling Cancer Magazine" Youth Editorial Committee

references:

[1] 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.

[2] Moro-Sibilot D, et al. Ann oncol. 2019; 30 (12): 1985-1991.

[3] wolf j, et al. N English. 2020; 383 (10): 944-957.

[4] Seung Tae Kim et al. Combination of Docetaxel Plus Savolitinib in Refractory Cancer Patients: a Report on Phase I Trial. 12 (4): 597-601.

[5] Lee J, Kim ST, Kim K, Et Al. Tumor Genomic Profiling Guides Patients with Metastatic Gastric Cancer to Targeted Treatment: The viktory umbrella trial. Cancer Discov.

[6] Landi L, Minuti G, D'Wececco A, et al Met Overexpression and Gene Amplification in NSCLC: A Clinical Perspective. LUNG CANCER (AUCKL). 2013; 4: 15-25.

[7] Ryan Hartmaier, Ji-YOUN Han, Byoung Chul Cho, et al. Tumor Response and Met-DETECT METHODS Exploatch Biomarker Analysis of the PART B TATTON Study. Acr 20211121, ABSTRR 20211, ABSTRR 20211, ABSTRR 20211, ABSTRR 20211, ABSTRR 20211, ABSTRR 20211, ABSTRR 20211, ABSTRER 20211, ABSTRER 202's, ABSTREA ’s

[8] Myung-ju Ahn, et al. Met Biomarker-Based Preliminary Effical Analysis in Savannah: Savolitinib+Osimertinib in EGFRC POSIMERTINIB., Do not represent the viewpoint of this platform

- END -