Savolitinib versus crizotinib for treating MET positive non-small cell lung cancer
Kang Miao1, Xiaotong Zhang1, Hanping Wang1
1Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Background:
The c-MET protein, encoded by the mesenchymal-epithelial transition factor (MET) gene, can regulate cell proliferation, migration and invasion. Studies have shown that it is one of the essential driver genes for non-small cell lung cancer (NSCLC). Currently, several clinical studies have carried out objective assessments on the efficacy and safety of different types of MET tyrosine kinase inhibitors (TKIs). However, direct cross-sectional comparisons between different agents are still not available.
Methods:
Our study was a single-center retrospective clinical study, which collected the data from MET positive NSCLC patients treated with MET TKIs at the Lung Cancer Center of Peking Union Medical College Hospital. We explored the efficacy and safety of crizotinib versus savolitinib in patients with METex14 skipping and MET amplification, separately.
Results:
Patients with METex14 skipping (median PFS = 10.7 months) had a better clinical response to MET TKIs than MET amplification patients (median PFS = 4.1 months). In the METex14 skipping subgroup, savolitinib did not show better survival benefit with significance than crizotinib (p > 0.05). In the MET amplification subgroup, savolitinib (median PFS = 7.1 months) demonstrated a better progression-free survival benefit than crizotinib (median PFS = 1.4 months), p = 0.05. The most common adverse effects of both MET TKIs were peripheral edema (41.2%), gastrointestinal reactions (23.5%), and liver injury (14.7%). The incidence rate of peripheral edema was higher in savolitinib than crizotinib.
Conclusion:
In METex14 skipping NSCLC patients, the efficacy of savolitinib and crizotinib did not show significant difference. In MET amplification patients, savolitinib showed better efficacy than crizotinib.
Insights
Savolitinib and crizotinib show similar efficacy in non-small cell lung cancer (NSCLC) with METex14 skipping. However, savolitinib demonstrates superior progression-free survival over crizotinib in NSCLC patients with MET amplification.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- The c-MET protein, encoded by the MET gene, regulates cell proliferation, migration, and invasion, and is an essential driver in non-small cell lung cancer (NSCLC).
- MET tyrosine kinase inhibitors (TKIs) are clinically assessed for efficacy and safety in NSCLC.
- Direct comparative studies between different MET TKIs are lacking.
Purpose of the Study:
- To compare the efficacy and safety of crizotinib versus savolitinib in MET-positive NSCLC patients.
- To analyze treatment outcomes separately for METex14 skipping and MET amplification subtypes.
Main Methods:
- A single-center retrospective clinical study.
- Data collected from MET-positive NSCLC patients treated with MET TKIs.
- Comparison of crizotinib and savolitinib in METex14 skipping and MET amplification cohorts.
Main Results:
- METex14 skipping patients (median PFS 10.7 months) responded better to MET TKIs than MET amplification patients (median PFS 4.1 months).
- No significant difference in survival benefit between savolitinib and crizotinib in METex14 skipping NSCLC (p > 0.05).
- Savolitinib showed improved progression-free survival (median PFS 7.1 months) compared to crizotinib (median PFS 1.4 months) in MET amplification NSCLC (p = 0.05).
- Common adverse effects included peripheral edema, gastrointestinal reactions, and liver injury, with higher incidence of peripheral edema in savolitinib users.
Conclusions:
- Savolitinib and crizotinib exhibit comparable efficacy in METex14 skipping NSCLC.
- Savolitinib demonstrates superior efficacy compared to crizotinib in MET amplification NSCLC.
- Peripheral edema is a notable side effect associated with both MET TKIs.
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