Professor Lu Shun led the severtinib study on the international academic stage for the third time, bringing super long-term survival data

*For reference only for medical professionals Sivotinib is the only MET-TKI approved in China for the indication of MET exon 14 skipping mutation
.

The 2022 European Lung Cancer Congress (ELCC) will be held online from March 30 to April 2
.

The Phase II clinical study of sevolitinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutation, led by Professor Lu Shun of the Chest Hospital Affiliated to Shanghai Jiaotong University, was successfully selected for the 2022 ELCC oral report.
Final overall survival (OS) results were presented for the first time at the meeting
.

Studies have shown that sevolitinib can achieve a median overall survival (mOS) of 12.
5 months in the total population with MET exon 14 skipping mutations, and the safety is controllable.
Brain metastases and other subgroups have shown significant survival benefits [1]
.

Professor Lu Shun orally reported that sivotinib has appeared on the international stage for many times, bringing a new option for MET-targeted therapy.
The phase II clinical study of sivotinib [2] was led by Professor Lu Shun and carried out in 32 hospitals across the country
.

A total of 70 patients with locally advanced or metastatic MET exon 14 skipping mutation and histologically PSC or other NSCLC subtypes were included in the study
.

Patients who have received at least one round of systemic therapy (or intolerance) before, and have disease progression or can not tolerate treatment toxicity, receive sivotinib (body weight ≥ 50kg dose: 600mg, body weight <50kg dose: 400mg), each time Once a day, a 21-day cycle is administered until disease progression or intolerable toxicity occurs
.

Severotinib Study Design Baseline Characteristics of the Study Population Sivotinib has previously made several international appearances, including at the 2019 American Association for Cancer Research (AACR) Annual Meeting, with positive results from Phase II clinical studies , 2020 American Society of Clinical Oncology (ASCO) annual meeting, and the full text of the research was published in the international authoritative academic journal "The Lancet Respiratory Medicine"
.

In 2021, civotinib was approved for locally advanced or metastatic NSCLC with MET exon 14 skipping mutation, becoming the first and currently only MET inhibitor approved for marketing in China
.

The 2021 edition of the Chinese Society of Clinical Oncology (CSCO) NSCLC guidelines [3] gave a class II recommendation for savatinib
.

2022 ELCC: The final OS and subgroup analysis results were unveiled, and savatinib was effective and refractory to treatment.
At the 2022 ELCC, Professor Lu Shun orally reported the latest OS data and subgroup analysis results of the savatinib clinical study [1] ]
.

The overall population mOS was 12.
5 months in the savatinib study, and the savatinib survival benefit study showed that in the full analysis set (FAS), the median progression-free survival (mPFS) assessed by the investigator was 6.
9 Month, 12 and 15 months PFS rates were 31% and 25%, respectively; mOS was 12.
5 months, 18 months and 24 months OS rates were 42% and 31%, respectively; and sevolitinib was effective Rapid, median time to onset of action was 1.
4 months
.

The study included a high proportion of patients with very poor prognosis in advanced age (≥75 years: 23%), PSC (36%), brain metastases (21%), and previously treated (60%) patients, and still achieved 12.
5 months The mOS is very rare
.

As the first MET-TKI to report OS data, savatinib has a significant survival benefit
.

The mOS of PSC and other NSCLC populations was 10.
6 and 17.
3 months, bringing breakthroughs for patients with different subtypes.
The study showed that the mPFS of the PSC subgroup was 5.
5 months, and the mOS was 10.
6 months; the objective response rate (ORR) was 50%, The disease control rate (DCR) was 90%, and the tumor response was significant, showing a consistent trend of benefit
.

Cavatinib is the only MET inhibitor for which there is currently data in the PSC population
.

Referring to the mPFS of about 2 months and the mOS of 4-8 months after first-line chemotherapy for advanced PSC in the past [4-7], the PFS and OS of sevolitinib are significantly beneficial, bringing a breakthrough for the treatment of PSC patients.

.

At the same time, although other NSCLC subgroups in this study had a high proportion of brain metastases and more late-line patients, the mPFS still reached 7.
0 months, and the mOS reached 17.
3 months
.

The mOS in the treated subgroup was 19.
4 months, and there were significant benefits in different lines.
The treated subgroup had a mPFS of 6.
9 months and a mOS of 19.
4 months; and the ORR in the treated population was currently the highest, reaching 52.
6%
.

The study confirmed the long-term survival benefit of sevolitinib treatment in the treated population, which also guaranteed later-line treatment
.

The mPFS in the treatment-naïve subgroup was 6.
9 months and the mOS was 10.
9 months
.

Compared with the treatment-naïve subgroup, the median age of patients in the treatment-naïve subgroup was higher (67.
7 years vs 74.
5 years), the proportion of patients ≥75 years was higher (10% vs 43%), and the proportion of patients with PSC was higher higher (29% vs 46%), and these patients tended to have worse outcomes
.

Therefore, the mOS of the treatment-naïve population in this study should be interpreted with caution, and it does not mean that the benefit of savatinib in treatment-naïve NSCLC patients is small
.

The brain metastases subgroup has a mOS of 17.
7 months, which confirms that the hard power data of savatinib into the brain shows that the brain metastases subgroup has a mPFS of 7.
0 months and a mOS of 17.
7 months; The tumor response in the brain metastases population was 64.
3% ORR and 100% DCR
.

Since savatinib is not a substrate of P-glycoprotein (P-gp), it is theoretically not easy to be excreted by the blood-brain barrier efflux pump and can maintain the drug concentration in the brain.
The patient laid a theoretical foundation
.

This study shows that sevolitinib has sufficient brain penetration and is currently the only MET inhibitor for which OS data in brain metastases have been observed
.

Cavatinib provides a treatment option for this subgroup of patients with poor prognosis and few treatment options [2]
.

In addition, the subgroup without brain metastases had a mPFS of 6.
2 months and an mOS of 10.
9 months
.

In the subgroup without brain metastases, the proportion of patients with PSC was 42%, more than three times that of the subgroup with brain metastases (13%)
.

The subgroup without brain metastases also had a higher proportion of patients with poor health status
.

This may be the reason for the relatively short mOS in this subgroup
.

Controllable safety profile With prolonged follow-up and increased exposure, the safety profile of sevolitinib treatment was favorable, and the incidence of adverse events (AEs) was similar to previously reported data and consistent across subgroups
.

Of these, 32 (45.
7%) patients reported grade ≥3 treatment-related AEs, the most common being elevated aspartate aminotransferase (AST) (12.
9%), elevated alanine aminotransferase (ALT) ( 10.
0%) and peripheral edema (8.
6%), no interstitial lung disease and no new AE signal
.

The safety results and conclusions of the severtinib study have opened up new frontiers in the field of MET diagnosis and treatment, and the future can be expected.
Professor Lu Shun said that the research and development of savatinib is very difficult.
, successfully listed
.

At present, sevolitinib is the only indication for MET exon 14 skipping mutation approved in China, the only 100% Chinese population with confirmed efficacy and a breakthrough in refractory treatment, the only MET-TKI independently developed in China recommended by the guidelines, and the only available MET-TKI in the Chinese market.
and highly selective MET-TKI
.

Since its launch more than half a year ago, sevolitinib has been widely used in clinical practice and has shown amazing curative effects
.

Even in the 90-year-old and refractory patients with liver transplantation, it has excellent efficacy and good safety
.

The phase II registration study of savatinib included 100% of the Chinese patient population.
The OS results were unveiled at the 2022 ELCC, which once again confirmed the long-term survival of sivotinib in the general NSCLC population, as well as in refractory PSC, treatment-experienced and brain metastases patients The advantages and good safety will further enhance the confidence of Chinese doctors and patients in the clinical use of savatinib, and also reflect the international recognition of the scientific research capabilities of Chinese scholars
.

It is hoped that savatinib can be included in medical insurance as soon as possible to benefit Chinese patients with rare target-mutated lung cancer
.

In addition to the MET exon 14 skipping mutation, sevolitinib is currently being explored for MET amplification, MET overexpression, MET fusion and other types of MET abnormalities
.

Looking forward to the release of the research results, bringing hope and dawn of long-term survival to more patients
.

Expert Profile Professor Lu Shun Chief Physician, Doctoral Supervisor, Second-level Professor, Young and Middle-aged Expert with Outstanding Contribution to National Health, Leading Talent in Shanghai, Outstanding Academic Leader in Shanghai, Chief Expert of National Key Special Project, enjoys special allowance from the State Council Shanghai Jiaotong University Affiliated Chest Hospital, Director of Shanghai Pulmonary Cancer Clinical Center Member of Academic Committee of Shanghai Jiaotong University School of Medicine Director of China Anti-Cancer Association, former Director of Lung Cancer Professional Committee Executive Director of Chinese Society of Clinical Oncology (CSCO), Vice President of Heathko Foundation Chairman of DIA China Advisory Committee Vice Chairman Former Chairman of Shanghai Medical Association Oncology Society Former Chairman of Shanghai Medical Association Oncology Association Standing Committee Member of Chinese Medical Association Oncology Association, Chairman of Lung Cancer Expert Committee Vice Chairman of Shanghai Medical Doctor Association Oncology Branch, Specialist Training Team Leader International Lung Cancer Research Association (IASLC) Publishing Committee Member, American Society of Clinical Oncology (ASCO) China Representative, Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer, Deputy Editor-in-Chief of Lung Cancer, Editor-in-Chief of The Oncologist, Executive Director of Shanghai Anti-Cancer Association Executive Director of China Medical Biotechnology Association The deputy director of the Medical Branch, as the person in charge, presided over the national key projects of chronic diseases and international cooperation projects of the Ministry of Science and Technology; the national new drug innovation major project, 2 sub-projects of 863 major projects; the key projects of the National Natural Science Foundation of China and the general project China Anti-Cancer Association Science and Technology Award First prize; First prize of Shanghai Medical Science and Technology Award; Second prize of Huaxia Medical Science and Technology Award; First prize of Shanghai Science and Technology Progress; 2021 "WuXi AppTec Life Chemistry Research Award" References: [1].
Lu S et al.
(2022) Final OS results and subgroup analysis of savolitinib in patients with MET exon 14 skipping mutations (METex14+) NSCLC.
Oral presentation at the 2022 European Lung Cancer Conference, Prague, The Czech Republic.
[2].
Lu S, 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.
Lancet Respir Med.
2021 Jun 21: S2213-2600(21)00084-9.
doi: 10.
1016/S2213-2600(21)00084-9.
[3].
Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Non-Small Cell Lung Cancer 2021 Edition.
[4].
Bae HM , et al.
“Palliative chemotherapy for pulmonary pleomorphic carcinoma”Lung Cancer.
2007 Oct;58(1):112-5.
[5].
Hong, JY , et al.
"Palliative chemotherapy for non-transitional cell carcinomas of the urothelial tract.
" Medical Oncology (2009).
[6].
Vieira T, Girard N, Ung M, et al.
Efficacy of first-line chemotherapy in patients with advanced lung sarcomatoid carcinoma.
J Thorac Oncol 2013; 8: 1574–77.
[7].
Ung, M.
, et al.
"Characteristics and Clinical Outcomes of Sarcomatoid Carcinoma of the Lung.
" Clinical Lung Cancer (2016):391-397.
[1].
Lu S et al.
(2022) Final OS results and subgroup analysis of savolitinib in patients with MET exon 14 skipping mutations (METex14+) NSCLC.
Oral presentation at the 2022 European Lung Cancer Conference, Prague, The Czech Republic.
[2].
Lu S, 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.
Lancet Respir Med.
2021 Jun 21:S2213-2600(21)00084-9.
doi: 10.
1016/S2213-2600( 21)00084-9.
[3].
Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Non-Small Cell Lung Cancer 2021 Edition.
[4].
Bae HM, et al.
“Palliative chemotherapy for pulmonary pleomorphic carcinoma”Lung Cancer.
2007 Oct; 58(1):112-5.
[5].
Hong, JY, et al.
"Palliative chemotherapy for non-transitional cell carcinomas of the urothelial tract.
" Medical Oncology (2009).
[6].
Vieira T, Girard N, Ung M, et al.
Efficacy of first-line chemotherapy in patients with advanced lung sarcomatoid carcinoma.
J Thorac Oncol 2013; 8: 1574–77.
[7].
Ung, M.
, et al.
"Characteristics and Clinical Outcomes of Sarcomatoid Carcinoma of the Lung.
" Clinical Lung Cancer (2016):391-397.
*This article It is only used to provide scientific information to medical professionals and does not represent the views of this platformClinical Lung Cancer (2016): 391-397.
*This article is only for providing scientific information to medical professionals and does not represent the views of this platformClinical Lung Cancer (2016): 391-397.
*This article is only for providing scientific information to medical professionals and does not represent the views of this platform