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Impact of a planned dose interruption of dacomitinib in the treatment of advanced non-small-cell lung cancer (ARCHER 1042)

 Dong-Wan Kim  ;  Edward B. Garon  ;  Aminah Jatoi  ;  Dorothy M. Keefe  ;  Mario E. Lacouturee  ;  Stephen Sonis  ;  Diana Gernhardt  ;  Tao Wangg  ;  Nagdeep Giri  ;  Jim P. Doherty  ;  Sashi Nadanaciva  ;  Joseph O’Connell  ;  Eric Sbar  ;  Byoung Chul Cho 
 LUNG CANCER, Vol.106 : 76-82, 2017 
Journal Title
Issue Date
Carcinoma, Non-Small-Cell Lung/drug therapy* ; Cohort Studies ; Disease-Free Survival ; Dose-Response Relationship, Drug* ; Female ; Humans ; Lung Neoplasms/drug therapy* ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Quinazolines/therapeutic use ; Quinazolinones/administration & dosage ; Quinazolinones/adverse effects ; Quinazolinones/blood* ; Quinazolinones/pharmacokinetics ; Receptor, Epidermal Growth Factor/antagonists & inhibitors ; Receptor, Epidermal Growth Factor/genetics ; Republic of Korea ; Treatment Outcome
Dacomitinib ; Dose interruption ; Non-small-cell lung cancer ; Pharmacokinetic ; Supportive care
OBJECTIVES: Dacomitinib is a pan-HER inhibitor for advanced non-small-cell lung cancer (NSCLC). We explored the impact of a planned 4-day dacomitinib dose interruption on plasma exposure of dacomitinib and adverse events (AEs) of interest in Cohort III of the ARCHER 1042 study.

MATERIALS AND METHODS: Patients, treatment-naïve for advanced NSCLC with EGFR activating mutations, received oral dacomitinib 45mg QD (once daily). A planned dose interruption occurred in Cycle 1 from Days 11 through 14. The primary endpoint was the pharmacokinetic (PK) characteristics of dacomitinib in Cycle 1Day 10 and during dose interruption. Secondary endpoints included safety and concomitant medications used to treat AEs of interest.

RESULTS: Cohort III enrolled 25 patients. Median plasma Cmax of dacomitinib in Cycle 1 Day 10 was 83.40ng/mL. Average median plasma dacomitinib concentration during the 4-day dose interruption was 42.63ng/mL. In the first 8 weeks of treatment 1) 80% of patients used concomitant medications for dermatologic AEs, 76% for diarrhea, and 44% for stomatitis, and 2) all patients experienced treatment-emergent AEs and 28% had all-causality Grade 3 AEs.

CONCLUSION: At 45mg QD dosing, PK parameters of plasma dacomitinib in Cycle 1 Day 10 were comparable to that obtained in Cycle 1 Day 14 from other dacomitinib studies. Average median plasma dacomitinib concentration during the 4-day dose interruption was approximately half of the median plasma Cmax of dacomitinib observed prior to dose interruption. The toxicity profile was consistent with that from other studies of dacomitinib.
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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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