Clinical Activity And Safety Profile Of Dacomitinib In Advanced Epidermal Growth Factor Receptor-Positive Non-Small Cell Lung Cancer Patients With Brain Metastases.

e21656 Background: Dacomitinib is a second-generation epidermal growth factor receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) which has been shown to be superior to first-generation EGFR TKI, gefitinib in both progression- free survival and overall survival outcomes in EGFR+, non-small cell lung cancer (NSCLC) patients in a Phase III, randomized study, ARCHER 1050. However, the activity of dacomitinib in the central nervous system (CNS) is not known as ARCHER 1050 did not include patients with baseline brain metastases (BM). To our knowledge, this is the first chart review which describes dacomitinib’s activity in the CNS in a real-world setting. Methods: 24 patients who were receiving dacomitinib (30 mg daily) for advanced NSCLC harboring EGFR sensitive mutations, either Exon 19 deletion or Exon 21 L858R substitutions were included in this study. Hospital chart was retrospectively reviewed to identify patients with baseline brain metastases (n = 6). Treatment outcomes of these patients who were presented with baseline brain metastasis were analyzed. Results: Among the 6 patients, median age was 54.5 years (range, 41-74), 4 were male, ECOG PS 0 and 1 were 1 and 5, respectively. All of them had non-squamous NSCLC with asymptomatic BM and 5 with no measurable BM lesion. One patient had dose reduction due to drug-related adverse events. One patient has not reached the 4-week RECIST assessment at data cut-off. The intracranial ORR and DCR among 5 response- evaluable patients with at least one follow-up disease assessment were 40% and 100% (2/5 complete response, 3/5 stable disease). All patients are having ongoing treatment (median follow-up:3-months). Patients experienced low-grade (G1/2) toxicities which are reversible, including diarrhea, rash, paronychia and stomatitis. Conclusions: This chart review suggests, for the first-time, that dacomitinib may have CNS efficacy in patients with untreated EGFR+ NSCLC in the real-world setting. Due to the small number of patients included in this chart review, the findings need to be confirmed in future studies.