Comparative Toxicovigilance of Capmatinib and Tepotinib in NSCLC: Respiratory Signal Detection and Adverse Event
Xing Chang1, Danyan Shao1, Jianan Bao1
1Department of Pharmacy, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Center of Soochow University, Suzhou, China.
Abstract:
Capmatinib and tepotinib are selective MET inhibitors for MET exon 14 skipping non-small cell lung cancer (NSCLC), yet comprehensive real-world safety profiles, particularly concerning respiratory and rare adverse events (AEs), remain limited. We conducted a disproportionality analysis of the FDA AE Reporting System (FAERS) database, utilizing four algorithms (ROR, PRR, BCPNN, MGPS) to identify AE signals from 1771 cases for capmatinib and 470 for tepotinib, standardized with MedDRA v26.0. Both inhibitors shared signals for systemic AEs, such as peripheral oedema and gastrointestinal disorders. However, their respiratory AE profiles diverged: capmatinib was associated with pleural effusion and pulmonary oedema, whereas tepotinib was linked to infectious complications, including interstitial lung disease and infectious pleural effusion. Importantly, we identified significant novel signals beyond current drug labels: sensory disturbances, and thrombosis for capmatinib; and fluid imbalance-related events for tepotinib. These distinct AE profiles highlight an infection-driven pulmonary risk for tepotinib requiring close monitoring, while capmatinib's association with sensory disorders warrants specific patient management considerations. Our findings underscore the need for individualized safety monitoring based on the unique AE profiles of each MET inhibitor.
Insights
Capmatinib and tepotinib, MET inhibitors for non-small cell lung cancer (NSCLC), show distinct safety profiles. Capmatinib risks include sensory issues, while tepotinib may cause infection-related lung problems, necessitating tailored monitoring.
Area of Science:
- Pharmacovigilance
- Oncology
- Drug Safety
Background:
- Selective MET inhibitors capmatinib and tepotinib treat MET exon 14 skipping non-small cell lung cancer (NSCLC).
- Real-world safety data, especially for respiratory and rare adverse events (AEs), are limited for these targeted therapies.
Purpose of the Study:
- To conduct a comprehensive real-world safety analysis of capmatinib and tepotinib.
- To identify and compare specific adverse event profiles, focusing on respiratory and rare events, using a large safety database.
Main Methods:
- Disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database.
- Utilized four algorithms (ROR, PRR, BCPNN, MGPS) to detect AE signals for capmatinib (1771 cases) and tepotinib (470 cases).
- Standardized events using Medical Dictionary for Regulatory Activities (MedDRA) v26.0.
Main Results:
- Both drugs showed signals for systemic AEs like peripheral edema and gastrointestinal disorders.
- Distinct respiratory AE profiles emerged: capmatinib linked to pleural effusion and pulmonary edema; tepotinib associated with infectious complications (e.g., interstitial lung disease, infectious pleural effusion).
- Novel signals identified: sensory disturbances and thrombosis for capmatinib; fluid imbalance events for tepotinib.
Conclusions:
- Tepotinib presents an infection-driven pulmonary risk requiring close monitoring.
- Capmatinib's association with sensory disorders necessitates specific patient management strategies.
- Individualized safety monitoring is crucial due to the unique AE profiles of each MET inhibitor.
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