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

Research output: Contribution to journalArticle

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Abstract

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
Volume9
Issue number10
DOIs
Publication statusPublished - 2014 Oct 1

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Non-Small Cell Lung Carcinoma
Safety
Drug Therapy
Confidence Intervals
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Disease-Free Survival
Pharmacokinetics
Paronychia
Erlotinib Hydrochloride
PF 00299804
gefitinib
Dermatitis
Therapeutics
Patient Safety
Cough
Disease Progression
Diarrhea
Adenocarcinoma
Pain

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Park, Keunchil ; Cho, Byoung C. ; Kim, Dong Wan ; Ahn, Myung Ju ; Lee, Sang Yoon ; Gernhardt, Diana ; Taylor, Ian ; Campbell, Alicyn K. ; Zhang, Hui ; Giri, Nagdeep ; Letrent, Stephen P. ; O'Connell, Joseph ; Heo, Dae S. / 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. In: Journal of Thoracic Oncology. 2014 ; Vol. 9, No. 10. pp. 1523-1531.
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abstract = "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.",
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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. / Park, Keunchil; Cho, Byoung C.; Kim, Dong Wan; Ahn, Myung Ju; Lee, Sang Yoon; Gernhardt, Diana; Taylor, Ian; Campbell, Alicyn K.; Zhang, Hui; Giri, Nagdeep; Letrent, Stephen P.; O'Connell, Joseph; Heo, Dae S.

In: Journal of Thoracic Oncology, Vol. 9, No. 10, 01.10.2014, p. 1523-1531.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

T2 - A phase I/II trial

AU - Park, Keunchil

AU - Cho, Byoung C.

AU - Kim, Dong Wan

AU - Ahn, Myung Ju

AU - Lee, Sang Yoon

AU - Gernhardt, Diana

AU - Taylor, Ian

AU - Campbell, Alicyn K.

AU - Zhang, Hui

AU - Giri, Nagdeep

AU - Letrent, Stephen P.

AU - O'Connell, Joseph

AU - Heo, Dae S.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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.

AB - 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.

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