title: Impact of a planned dose interruption of dacomitinib in the treatment of advanced non-small-cell lung cancer (ARCHER 1042).
abstract: 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.
  
  
  
  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.
  
  
  
  Cohort III enrolled 25 patients. Median plasma Cmaxof 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.
  
  
  
  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 Cmaxof dacomitinib observed prior to dose interruption. The toxicity profile was consistent with that from other studies of dacomitinib.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. Electronic address: kimdw@snu.ac.kr.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Garon
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Aminah
authors.initials: A
authors.lastname: Jatoi
authors.affiliation: University of Adelaide, Adelaide, Australia.
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: Keefe
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Mario E
authors.initials: ME
authors.lastname: Lacouture
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Sonis
authors.affiliation: Pfizer Oncology, Groton, CT, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Gernhardt
authors.affiliation: Pfizer Oncology, Groton, CT, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Pfizer Oncology, La Jolla, CA, USA.
authors.forename: Nagdeep
authors.initials: N
authors.lastname: Giri
authors.affiliation: Pfizer Oncology, New York, NY, USA.
authors.forename: Jim P
authors.initials: JP
authors.lastname: Doherty
authors.affiliation: Pfizer Oncology, Groton, CT, USA.
authors.forename: Sashi
authors.initials: S
authors.lastname: Nadanaciva
authors.affiliation: Pfizer Oncology, New York, NY, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: O'Connell
authors.affiliation: Pfizer Oncology, Collegeville, PA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Sbar
authors.affiliation: Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Cho
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D015331:Cohort Studies; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011799:Quinazolines / Q000627:therapeutic use; D052999:Quinazolinones / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics; D056910:Republic of Korea; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D052999:Quinazolinones; C525726:dacomitinib; D066246:ErbB Receptors
keywords: Dacomitinib; Dose interruption; Non-small-cell lung cancer; Pharmacokinetic; Supportive care