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Safety and efficacy of dacomitinib in korean patients with KRAS wild-type advanced non-small-cell lung cancer refractory to chemotherapy and erlotinib or gefitinib: a phase I/II trial.

 Keunchil Park  ;  Byoung C. Cho  ;  Dong Wan Kim  ;  Myung Ju Ahn  ;  Sang Yoon Lee  ;  Diana Gernhardt  ;  Ian Taylor  ;  Alicyn K. Campbell  ;  Hui Zhang  ;  Nagdeep Giri  ;  Stephen P. Letrent  ;  Joseph O’Connell  ;  Dae S. Heo 
 JOURNAL OF THORACIC ONCOLOGY, Vol.9(10) : 1523-1531, 2014 
Journal Title
Issue Date
Adenocarcinoma/drug therapy* ; Adenocarcinoma/enzymology ; Adenocarcinoma/genetics ; Adenocarcinoma/pathology ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Biomarkers, Pharmacological/metabolism ; Drug Resistance, Neoplasm ; Erlotinib Hydrochloride ; Female ; Genes, ras* ; Humans ; Lung Neoplasms/drug therapy* ; Lung Neoplasms/enzymology ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Protein Kinase Inhibitors/adverse effects ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins p21(ras) ; Quinazolines/pharmacology ; Quinazolinones/adverse effects ; Quinazolinones/therapeutic use* ; Republic of Korea ; Treatment Outcome ; ras Proteins/genetics
Dacomitinib ; Non–small-cell lung cancer ; Erlotinib ; Gefitinib ; Refractory
INTRODUCTION: Dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor ([HER]-1/EGFR, HER-2, and HER-4) tyrosine kinase inhibitor, demonstrated antitumor activity in Western patients with non-small-cell lung cancer (NSCLC) at a dose of 45 mg once daily. We report data from a phase I/II, multicenter, open-label study of Korean patients with refractory KRAS wild-type adenocarcinoma NSCLC (defined as patients with evidence of disease progression during or within 6 months of treatment with chemotherapy and gefitinib or erlotinib).
METHODS: The phase I dose-finding portion identified the recommended phase II dose (RP2D) in Korean patients, evaluated safety, and characterized the pharmacokinetics of dacomitinib. In the phase II portion, patients received dacomitinib at the RP2D. The primary end point was progression-free survival at 4 months (PFS4m).
RESULTS: Twelve patients enrolled in phase I, and 43 patients enrolled in phase II at the RP2D of 45 mg once daily. In phase II, PFS4m was 47.2% (95% confidence interval [CI], 31.6-61.3; one-sided p-value = 0.0007). Median PFS was 15.4 weeks (95% CI, 9.7-17.6); median overall survival was 46.3 weeks (95% CI, 32.7-not reached); and the objective response rate was 17.1% (95% CI, 7.2-32.1). Common treatment-related adverse events were dermatitis acneiform, diarrhea, and paronychia; there were no treatment-related grade 4 or 5 adverse events. Pharmacokinetic parameters of dacomitinib in Korean patients were similar to those reported in Western patients. By patient report, NSCLC symptoms "cough" and "pain" showed improvement within 3 weeks of initiating treatment.
CONCLUSIONS: Dacomitinib was well tolerated and had antitumor activity in Korean patients with NSCLC who had previously progressed on chemotherapy and an epidermal growth factor receptor tyrosine kinase inhibitor.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
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