The pharmacokinetics of capmatinib and its efficacy in non-small cell lung cancer treatment: a narrative review.

BACKGROUND AND OBJECTIVE

Inhibitors of mesenchymal-epithelial transition () receptor serve as significant therapeutic agents in -driven non-small cell lung cancer (NSCLC). Among these, capmatinib has demonstrated particularly notable efficacy and safety. However, the mechanisms responsible for its benefit remain unclear. This narrative review presents the pharmacokinetics (PK)-related evidence regarding the efficacy of inhibitors for NSCLC and examines the differences in capmatinib as compared to other type Ib inhibitors.

METHODS

We conducted an exhaustive search of the English-language literature on inhibitors in NSCLC published or presented from June 2010 to February 2025 in the PubMed and Foreign Medical Literature Retrieval Service (FMRS; China) databases. It also included literature presented at various international meetings. The key literatures were identified from this search. Further, the clinical PK and clinical efficacy of type Ib inhibitors were analyzed.

KEY CONTENT AND FINDINGS

The review provides a comparison of the PK for type Ib inhibitors in clinical practice. Specifically, capmatinib is absorbed more quickly in humans and exhibits the highest level of exposure compared to other inhibitors. Capmatinib has greater efficacy as assessed via the ratio of half maximal inhibitory concentration, and there is no requirement for dosage adjustment based on any level of hepatic impairment. Capmatinib has a faster clearance time, minimizing the likelihood of accumulation and the occurrence of adverse events (AEs). Its exposure levels are minimally impacted by food intake and drug-drug interaction. Capmatinib has a good PK profile after combination with gefitinib, constituting a promising option for patients with epidermal growth factor receptor ()-mutated NSCLC. Moreover, capmatinib exerts marked effects for brain metastases (BMs) in patients with NSCLC due its lipophilicity and permeability. Furthermore, capmatinib and tepotinib demonstrate extraordinary efficacy for patients with NSCLC and exon 14 (ex14) skipping mutation, and the combination of capmatinib and gefitinib in particular can achieve remarkable therapeutic effects in patients with -mutated, -dysregulated (amplified/overexpressing) NSCLC.

CONCLUSIONS

inhibitors, especially capmatinib, are the preferred treatment choice for patients with NSCLC and ex14 mutation and BM. The administration of capmatinib can help mitigate potential food-intake and drug-drug interactions in clinical settings. This facilitates the optimization of long-term medication schedules, enhancing the clinical efficacy of the treatment.