What is the effect of dacomitinib/dacomitinib on brain metastasis?

Dacomitinib is a potent, irreversible pan-HER tyrosine kinase inhibitor (TKI) used to treat epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Currently, evidence of its activity against brain metastases is lacking.

Clinically, dacomitinib has also been studied in patients with non-small cell lung cancer who had enhanced MRI-detected brain metastases and laboratory-confirmed EGFR mutations before treatment. A total of 14 patients with EGFR-mutated NSCLC with brain metastases received first-line dacomitinib. The first imaging examinations of chest CT and brain MRI were performed one month later and every two months thereafter. Objective response rate (ORR) and depth of brain metastasis response were determined by RECIST 1.1 and RANO-LM criteria.

The results of the study showed that among 59 patients with EGFR mutated advanced non-small cell lung cancer who received first-line dacomitinib treatment, a total of 14 patients developed brain metastases before treatment. Of these patients, 5 patients received a starting dose of 45 mg of dacomitinib once daily, and 9 patients received 30 mg of dacomitinib once daily until disease progression or intolerable toxicity. Eight patients carried EGFR 19del, 5 patients carried EGFR L858R, and 1 patient carried EGFR G719A and I706 T co-mutations. The median follow-up time was 4.5 months. All patients were reviewed at least once. The effective rate is 92.9%, and the disease control rate (DCR) is 100%. Measurable responses in intracranial metastases were observed in 12 of 14 patients, including 12 of 13 patients with parenchymal brain metastases, but 1 patient with meningeal metastases had a poor response. All patients (100%) had grade 1-2 adverse reactions, but none discontinued treatment or required dose adjustment.

This case series of 14 patients shows that dakotinib is effective against central nervous system (CNS) metastasis in EGFR-positive non-small cell lung cancer. More data are needed to confirm its advantages and optimize its clinical application.