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. Lacouture, Stephen Sonis, Diana Gernhardt, Tao Wang, Nagdeep Giri, Jim P. Doherty, Sashi Nadanaciva, Joseph O'Connell, Eric Sbar, ByoungChul Cho

Research output: Contribution to journalArticle

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Abstract

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 45 mg 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 1 Day 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 83.40 ng/mL. Average median plasma dacomitinib concentration during the 4-day dose interruption was 42.63 ng/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 45 mg 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.

Original languageEnglish
Pages (from-to)76-82
Number of pages7
JournalLung Cancer
Volume106
DOIs
Publication statusPublished - 2017 Apr 1

Fingerprint

Non-Small Cell Lung Carcinoma
Therapeutics
PF 00299804
Pharmacokinetics
Stomatitis
Causality
Diarrhea
Safety
Mutation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Kim, Dong Wan ; Garon, Edward B. ; Jatoi, Aminah ; Keefe, Dorothy M. ; Lacouture, Mario E. ; Sonis, Stephen ; Gernhardt, Diana ; Wang, Tao ; Giri, Nagdeep ; Doherty, Jim P. ; Nadanaciva, Sashi ; O'Connell, Joseph ; Sbar, Eric ; Cho, ByoungChul. / Impact of a planned dose interruption of dacomitinib in the treatment of advanced non-small-cell lung cancer (ARCHER 1042). In: Lung Cancer. 2017 ; Vol. 106. pp. 76-82.
@article{e8d2a25a44a947ea9c1652b31429c422,
title = "Impact of a planned dose interruption of dacomitinib in the treatment of advanced non-small-cell lung cancer (ARCHER 1042)",
abstract = "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-na{\"i}ve for advanced NSCLC with EGFR activating mutations, received oral dacomitinib 45 mg 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 1 Day 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 83.40 ng/mL. Average median plasma dacomitinib concentration during the 4-day dose interruption was 42.63 ng/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 45 mg 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.",
author = "Kim, {Dong Wan} and Garon, {Edward B.} and Aminah Jatoi and Keefe, {Dorothy M.} and Lacouture, {Mario E.} and Stephen Sonis and Diana Gernhardt and Tao Wang and Nagdeep Giri and Doherty, {Jim P.} and Sashi Nadanaciva and Joseph O'Connell and Eric Sbar and ByoungChul Cho",
year = "2017",
month = "4",
day = "1",
doi = "10.1016/j.lungcan.2017.01.021",
language = "English",
volume = "106",
pages = "76--82",
journal = "Lung Cancer",
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Kim, DW, Garon, EB, Jatoi, A, Keefe, DM, Lacouture, ME, Sonis, S, Gernhardt, D, Wang, T, Giri, N, Doherty, JP, Nadanaciva, S, O'Connell, J, Sbar, E & Cho, B 2017, 'Impact of a planned dose interruption of dacomitinib in the treatment of advanced non-small-cell lung cancer (ARCHER 1042)', Lung Cancer, vol. 106, pp. 76-82. https://doi.org/10.1016/j.lungcan.2017.01.021

Impact of a planned dose interruption of dacomitinib in the treatment of advanced non-small-cell lung cancer (ARCHER 1042). / Kim, Dong Wan; Garon, Edward B.; Jatoi, Aminah; Keefe, Dorothy M.; Lacouture, Mario E.; Sonis, Stephen; Gernhardt, Diana; Wang, Tao; Giri, Nagdeep; Doherty, Jim P.; Nadanaciva, Sashi; O'Connell, Joseph; Sbar, Eric; Cho, ByoungChul.

In: Lung Cancer, Vol. 106, 01.04.2017, p. 76-82.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Impact of a planned dose interruption of dacomitinib in the treatment of advanced non-small-cell lung cancer (ARCHER 1042)

AU - Kim, Dong Wan

AU - Garon, Edward B.

AU - Jatoi, Aminah

AU - Keefe, Dorothy M.

AU - Lacouture, Mario E.

AU - Sonis, Stephen

AU - Gernhardt, Diana

AU - Wang, Tao

AU - Giri, Nagdeep

AU - Doherty, Jim P.

AU - Nadanaciva, Sashi

AU - O'Connell, Joseph

AU - Sbar, Eric

AU - Cho, ByoungChul

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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 45 mg 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 1 Day 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 83.40 ng/mL. Average median plasma dacomitinib concentration during the 4-day dose interruption was 42.63 ng/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 45 mg 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.

AB - 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 45 mg 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 1 Day 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 83.40 ng/mL. Average median plasma dacomitinib concentration during the 4-day dose interruption was 42.63 ng/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 45 mg 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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U2 - 10.1016/j.lungcan.2017.01.021

DO - 10.1016/j.lungcan.2017.01.021

M3 - Article

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AN - SCOPUS:85012044124

VL - 106

SP - 76

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JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

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