Phase 2 study of intermittent pulse dacomitinib in patients with advanced non-small cell lung cancers.

Abstract

BACKGROUND:

Dacomitinib is a second-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Pre-clinical data suggest that intermittent pulsatile dosing of dacomitinib may result in inhibition of EGFR T790M.

METHODS:

We evaluated safety, pharmacokinetics and efficacy of intermittent pulsatile dacomitinib in both molecularly unselected patients and patients with lung cancers harboring EGFR T790M (Clinical Trial Registration Number NCT01858389).

RESULTS:

Thirty-eight patients were treated on study with pulse dacomitinib; sixteen with EGFR T790M in Cohort A and 22 who were not molecularly selected in Cohort B. One patient out of 16 patients in Cohort A had a partial response to study therapy (ORR 6.3%, 95% CI 0.2-30.2%). The median progression-free survival (PFS) in Cohort A was 2.3 months and median PFS in Cohort B was 1.6 months. The adverse event profile was similar to standard daily dose dacomitinib with the most frequent treatment-related toxicities occurring in >20% of patients being diarrhea, rash, stomatitis, nausea, dry skin, paronychia, fatigue, and decreased appetite.

CONCLUSION:

Intermittent pulsatile dacomitinib is safe and relatively well tolerated but is not effective in patients that harbor EGFR T790M or in unselected patients with non-small cell lung cancer.

• Authors: Helena A Yu, Myung-Ju Ahn, Byoung Chul Cho, David E Gerber, Ronald B Natale, Mark A Socinski, Nagdeep Giri, Susan Quinn, Eric Sbar, Hui Zhang, Giuseppe Giaccone
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 112 Pg. 195-199 (10 2017) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 29191595 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Quinazolinones
• dacomitinib

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, pharmacokinetics)
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality, pathology)
• Female
• Humans
• Lung Neoplasms (drug therapy, mortality, pathology)
• Male
• Middle Aged
• Protein Kinase Inhibitors (administration & dosage, pharmacokinetics)
• Pulse Therapy, Drug
• Quinazolinones (administration & dosage, pharmacokinetics)