From the perspective of efficacy, which one is better, capmatinib or sivotinib?

Capmatinib and Savolitinib are both MET-targeted drugs that have attracted much attention in the precision treatment of non-small cell lung cancer (NSCLC) in recent years. Both are designed to target the specific driver gene abnormality of MET exon 14 skipping mutation. METex14 mutations are an important oncogenic pathway in non-small cell lung cancer, accounting for approximately 3-4% of NSCLC, and are particularly common in elderly patients, non-smokers, and lung adenocarcinoma and lung sarcomatoid carcinoma subtypes. With the widespread application of molecular subtyping in the treatment of lung cancer, there are increasing discussions surrounding the differences in efficacy between capmatinib and sarvotinib. If we analyze which of the two is better from the perspective of efficacy, we need to comprehensively compare its key clinical research data, objective response rate (ORR), progression-free survival (PFS), safety and practical application and other dimensions.

Capmatinib, developed by Novartis Pharmaceuticals, is the world's first MET-targeted inhibitor approved by the U.S.FDA. Its key registration clinical trial is the GEOMETRY mono-1 study, which is a multi-center, non-randomized, multi-cohort phase II study specifically evaluating the efficacy of capmatinib in METex14 mutation-positive NSCLC. In previously untreated patients, capmatinib achieved an objective response rate (ORR) of 68% and a median progression-free survival (PFS) of 12.4 months; in previously treated patients, the ORR was 41% and the PFS was 5.4 months. It is worth mentioning that capmatinib is also more active in patients with brain metastases and has a certain ability to penetrate the central nervous system. In addition, the drug has been approved by many countries, including the United States, Europe and China, and has been included in the recommendations of multiple international guidelines, such as NCCN and ESMO.

Sevotinib was jointly developed by AstraZeneca and related Chinese companies. It is the first MET inhibitor approved for marketing in China. It was approved by the National Medical Products Administration (NMPA) in 2021 for the treatment of patients with locally advanced or metastatic NSCLC with METex14 mutations. Its core clinical studies are multiple trials such as SAVANNAH and VIKTORY. Especially studies conducted in China show that among patients who have received systemic treatment, the ORR of saivotinib is 48.9%, the median PFS is 6.8 months, and the disease control rate (DCR) exceeds 90%. Although these data are slightly lower than those of capmatinib in untreated patients, saivotinib has better adaptability and tolerability in the East Asian population, and has certain accessibility advantages in the Chinese medical insurance system. At the same time, saivotinib is also currently exploring new indications in combination with EGFR-TKIs such as osimertinib to treat patients with mutations related to resistance mechanisms, and its clinical application prospects are broad.

From the data point of view, the objective response rate of capmatinib in first-line treatment andPFS is slightly advantageous, especially for patients with METex14 mutations who are first diagnosed and have a certain ability to control brain metastasis. Savotinib, on the other hand, has shown good stability and economic accessibility in local studies in China, and is more suitable for Chinese patients who have received systemic treatment and have barriers to accessing Western original drugs. From a mechanism perspective, both are selective MET inhibitors, but capmatinib is a type I inhibitor and sevotinib is a type II inhibitor. There may be slightly different target binding sites, which may explain the cross-resistance and individual differential responses of some patients to the two drugs.

Reference materials:https://www.novartis.com/our-products/pipeline/capmatinib