Keunchil Park1, 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. 1. *Division of Hematology & Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; †Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea; ‡Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; §Pfizer Korea, Seoul, Republic of Korea; ‖Pfizer Oncology, Groton, Connecticut; ¶Pfizer (China) Research & Development Co. Ltd, Shanghai, China; #Pfizer Oncology, La Jolla, California; and **Pfizer Oncology, New York, New York.
Abstract
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.
INTRODUCTION:Dacomitinib (PF-00299804), an irreversible pan-humanepidermal 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.
Authors: Dong-Wan Kim; Edward B Garon; Aminah Jatoi; Dorothy M Keefe; Mario E Lacouture; Stephen Sonis; Diana Gernhardt; Tao Wang; Nagdeep Giri; Jim P Doherty; Sashi Nadanaciva; Joseph O'Connell; Eric Sbar; Byoung Chul Cho Journal: Lung Cancer Date: 2017-02-01 Impact factor: 5.705
Authors: Jon Zugazagoitia; Asunción Díaz; Elisabeth Jimenez; Juan Antonio Nuñez; Lara Iglesias; Santiago Ponce-Aix; Luis Paz-Ares Journal: Front Med (Lausanne) Date: 2017-04-05
Authors: Niki Karachaliou; Manuel Fernandez-Bruno; Jillian Wilhelmina Paulina Bracht; Rafael Rosell Journal: Transl Cancer Res Date: 2019-01 Impact factor: 1.241