Dacomitinib induces objective responses in metastatic brain lesions of patients with EGFR-mutant non-small-cell lung cancer: A brief report

Abstract

Objective: Dacomitinib is a potent, irreversible and pan-HER tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Currently, evidence of its activity on brain metastasis is lacking.

Materials and methods: NSCLC patients diagnosed at Hunan Cancer Hospital between July, 2019 and July, 2020 with enhanced MRI-detected brain metastasis prior to treatment and laboratory-confirmed EGFR mutations were reviewed. In total, 14 EGFR-mutant NSCLC patients with brain metastasis were treated with first-line dacomitinib. The first radiographic review of chest CT and brain MRI was after one month and thereafter every 2 months. The objective response rate (ORR) and the depth of the brain metastasis response were determined via RECIST 1.1 and RANO-LM criteria.

Results: In total, 14 of 59 EGFR-mutant advanced NSCLC patients who received first-line dacomitinib therapy had brain metastasis before treatment. Among these patients, 5 were given a dacomitinib starting dose of 45 mg once daily, while 9 received 30 mg daily until disease progression or unbearable toxicity. Eight patients harbored EGFR 19del, 5 had EGFR L858R, and one patient had EGFR G719A and I706 T co-mutations. The median duration of follow-up was 4.5 months. All patients received at least one review. The ORR was 92.9 % (13/14) and the disease control rate (DCR) was 100 %. A measurable response of the intracranial metastases was observed in 12 of 14 patients (85.7 %), including 12 of 13 (92.3 %) with brain parenchymal metastasis, but the one patient with meningeal metastasis did not respond well. All patients (100 %) had grade 1-2 adverse effects, but none discontinued treatment or required a dosage adjustment.

Conclusions: This case series study of 14 patients has shown that dacomitinib has potent efficacy for central nervous system (CNS) metastasis in EGFR-positive NSCLC. More data are required to confirm its advantages and optimize its clinical application.

Keywords: Dacomitinib; EGFR mutations; Efficacy; Intracranial metastases; Non-small cell lung cancer; Tolerability.