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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)195-199
Number of pages5
JournalLung Cancer
Volume112
DOIs
Publication statusPublished - 2017 Oct

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Non-Small Cell Lung Carcinoma
Epidermal Growth Factor Receptor
Disease-Free Survival
Paronychia
Stomatitis
PF 00299804
Appetite
Exanthema
Protein-Tyrosine Kinases
Nausea
Fatigue
Diarrhea
Lung Neoplasms
Pharmacokinetics
Clinical Trials
Safety
Skin
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Yu, H. A., Ahn, M. J., Cho, B. C., Gerber, D. E., Natale, R. B., Socinski, M. A., ... Giaccone, G. (2017). Phase 2 study of intermittent pulse dacomitinib in patients with advanced non-small cell lung cancers. Lung Cancer, 112, 195-199. https://doi.org/10.1016/j.lungcan.2017.08.017
Yu, Helena A. ; Ahn, Myung Ju ; Cho, Byoung Chul ; Gerber, David E. ; Natale, Ronald B. ; Socinski, Mark A. ; Giri, Nagdeep ; Quinn, Susan ; Sbar, Eric ; Zhang, Hui ; Giaccone, Giuseppe. / Phase 2 study of intermittent pulse dacomitinib in patients with advanced non-small cell lung cancers. In: Lung Cancer. 2017 ; Vol. 112. pp. 195-199.
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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.",
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Yu, HA, Ahn, MJ, Cho, BC, Gerber, DE, Natale, RB, Socinski, MA, Giri, N, Quinn, S, Sbar, E, Zhang, H & Giaccone, G 2017, 'Phase 2 study of intermittent pulse dacomitinib in patients with advanced non-small cell lung cancers', Lung Cancer, vol. 112, pp. 195-199. https://doi.org/10.1016/j.lungcan.2017.08.017

Phase 2 study of intermittent pulse dacomitinib in patients with advanced non-small cell lung cancers. / Yu, Helena A.; Ahn, Myung Ju; Cho, Byoung Chul; Gerber, David E.; Natale, Ronald B.; Socinski, Mark A.; Giri, Nagdeep; Quinn, Susan; Sbar, Eric; Zhang, Hui; Giaccone, Giuseppe.

In: Lung Cancer, Vol. 112, 10.2017, p. 195-199.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase 2 study of intermittent pulse dacomitinib in patients with advanced non-small cell lung cancers

AU - Yu, Helena A.

AU - Ahn, Myung Ju

AU - Cho, Byoung Chul

AU - Gerber, David E.

AU - Natale, Ronald B.

AU - Socinski, Mark A.

AU - Giri, Nagdeep

AU - Quinn, Susan

AU - Sbar, Eric

AU - Zhang, Hui

AU - Giaccone, Giuseppe

PY - 2017/10

Y1 - 2017/10

N2 - 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.

AB - 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.

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