Wenying Peng1, Xingxiang Pu1, Meilin Jiang1, Jingyi Wang1, Jia Li1, Kang Li1, Yan Xu1, Fang Xu1, Bolin Chen1, Qianzhi Wang1, Jun Cao1, Yong Chen2, Lin Wu3. 1. The Second Department of Thoracic Oncology, Hunan Cancer Hospital / The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410000, PR China. 2. Department of Oncology, The Central Hospital of Shaoyang City, No. 36, Qianyuan Alley, Shaoyang, 422000, PR China. 3. The Second Department of Thoracic Oncology, Hunan Cancer Hospital / The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410000, PR China. Electronic address: wulin-calf@yeah.net.
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.
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:NSCLCpatients 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 NSCLCpatients 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 NSCLCpatients 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 EGFRL858R, and one patient had EGFRG719A 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.