Capmatinib for METex14 NSCLC: Test First, Monitor Toxicity

　　1.Who It Is For

　　Capmatinib is an oral MET tyrosine kinase inhibitor.

　　Indication boundary:

　　adult NSCLC;

　　locally advanced or metastatic;

　　confirmed MET exon 14 skipping mutation;

　　not empirical for all lung cancer.

　　METex14 occurs in~2%–4%of NSCLC,more often in older,less-smoking,adeno/sarcomatoid subtypes.

　　2.Testing First

　　prefer tumor tissue NGS covering MET splice region;

　　plasma ctDNA acceptable;if negative but suspected,retest tissue;

　　check MET amplification/resistance mutations when relevant;

　　no mutation confirmation→do not start.

　　3.Dosing

　　400mg orally twice daily;

　　with/without food,swallow whole;

　　miss or vomit a dose:skip,next dose on schedule;

　　titrate down 400→300→200mg twice daily per toxicity;

　　below 200mg BID not well studied.

　　Hepatic/renal:

　　mild/moderate/severe hepatic impairment:usually no change;

　　mild/moderate renal:usually no change;

　　severe renal:limited data,caution.

　　4.Efficacy Context

　　Tumor shrinkage seen in treatment-naïve and previously treated patients;some intracranial activity.

　　But:

　　response≠cure;

　　trial populations differ;

　　resistance via MET secondary mutations or bypass pathways;

　　ongoing imaging needed.

　　5.Common Reactions

　　peripheral edema;

　　nausea,vomiting;

　　fatigue,decreased appetite;

　　creatinine rise;

　　dyspnea,cough;

　　musculoskeletal pain.

　　6.Serious Warnings

　　ILD/pneumonitis

　　New/worsening cough,dyspnea,fever,hypoxia→hold drug;if no alternative cause,discontinue permanently.

　　Hepatotoxicity

　　LFTs at baseline,every 2 weeks for first 3 months,then monthly.Transaminase with bilirubin rise→hold/stop.

　　Photosensitivity

　　Sun protection,protective clothing,sunscreen.

　　Edema

　　Marked limb swelling,rapid weight gain→assess dose reduction.

　　Pancreatic/lab

　　Lipase,amylase,creatinine,albumin monitoring.

　　7.Interactions

　　avoid strong CYP3A inhibitors unless closely monitored;

　　avoid strong CYP3A inducers;

　　use moderate inducers cautiously;

　　review all concomitant drugs.