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

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18 Citations (Scopus)


Introduction: Dacomitinib (PF-00299804), an irreversible panhuman 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.

Original languageEnglish
Pages (from-to)1523-1531
Number of pages9
JournalJournal of Thoracic Oncology
Issue number10
Publication statusPublished - 2014 Oct 1

Bibliographical note

Funding Information:
Disclosure: Dr. Park has served as an advisor for Pfizer, AstraZeneca, Roche, Boehringer-Ingelheim, Eli Lilly, and Merck. Dr. Cho has received lecture fees from AstraZeneca and Pfizer, research funding from AstraZeneca and Sanofi-Aventis, and consulting fees from Bayer/Onyx. Dr. Kim has served as a consultant for Pfizer and has received honoraria from Pfizer. Drs. Lee, Gernhardt, Taylor, Zhang, Giri, and O’Connell are employees of Pfizer and have stock ownership with Pfizer. Drs. Campbell and Letrent are former employees of Pfizer and had stock ownership with Pfizer during the period of this employment. All other authors declare no conflict of interest.

Funding Information:
We thank all the participating patients and their families, and the network of investigators, research nurses, study coordinators, and operation staffs. Medical writing/editorial support was provided by Rachel Mason and Christine Arris at ACUMED (Tytherington, United Kingdom) with funding from Pfizer Inc. This study was sponsored by Pfizer Inc.

Publisher Copyright:
Copyright © 2014 by the International Association for the Study of Lung Cancer.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine


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