Phase II clinical and exploratory biomarker study of dacomitinib in patients with recurrent and/or metastatic squamous cell carcinoma of head and neck

Han Sang Kim, Hyeong Ju Kwon, Inkyung Jung, Mi Ran Yun, Myung Ju Ahn, Byung Woog Kang, Jong Mu Sun, Sung Bae Kim, Dok Hyun Yoon, Keon Uk Park, Se Hoon Lee, Yoon Woo Koh, Se Hun Kim, Eun Chang Choi, Dong Hoe Koo, Jin Hee Sohn, Bomi Kim, Nak Jung Kwon, Hwan Jung Yun, Min Goo LeeJi Hyun Lee, Tae Min Kim, Hye Ryun Kim, Joo Hang Kim, Soonmyung Paik, Byoung Chul Cho

Research output: Contribution to journalArticle

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Abstract

Purpose: The goals of this study were to investigate the clinical activity, safety, and biomarkers of dacomitinib, an irreversible tyrosine kinase inhibitor of EGFR, HER2, and HER4, in recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN). Experimental Design: Patients were eligible if the diseases were not amenable to curative treatment and had progressed on platinum-based chemotherapy, and were treated with dacomitinib 45 mg/day. The primary endpoint was objective response rate by RECISTv1.1. Exploratory analysis included the characterization of somatic mutation, gene copy number, gene expression, p16INK4A expression by IHC, and investigation of their relationship with clinical outcomes. Results: Forty-eight patients were evaluable for efficacy and toxicity. Ten patients (20.8%) had partial responses and 31 patients (65%) had stable diseases. The median progressionfree survival (PFS) and overall survival (OS) were 3.9 months [95% confidence interval (CI), 2.9-5.0] and 6.6 months (95% CI, 5.4-10.3). Adverse events were mostly grade 1-2. Mutations in the PI3K pathway (PIK3CA, PTEN ) and high expression of inflammatory cytokines (IL6, IL8, IL1A, IL1B, IL4, and TNF) were significantly associated with shorter PFS (2.9 vs. 4.9 months without mutations, P = 0.013; 2.8 vs. 9.9 months with low expression, P = 0.004). Those harboring PI3K pathway mutations or high inflammatory cytokine expression had shorter median OS (6.1 vs. 12.5 months lacking PI3K pathway mutations and with low inflammatory cytokine expression, P = 0.005). Conclusions: Dacomitinib demonstrated clinical efficacy with manageable toxicity in platinum-failed R/M-SCCHN patients. Screening of PI3K pathway mutation and inflammatory cytokine expression may help identify which R/M-SCCHN patients are likely to gain benefit from dacomitinib.

Original languageEnglish
Pages (from-to)544-552
Number of pages9
JournalClinical Cancer Research
Volume21
Issue number3
DOIs
Publication statusPublished - 2015 Feb 1

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Biomarkers
Phosphatidylinositol 3-Kinases
Mutation
Cytokines
Survival
Platinum
Confidence Intervals
Gene Dosage
Interleukin-8
Interleukin-4
Protein-Tyrosine Kinases
Carcinoma, squamous cell of head and neck
PF 00299804
Interleukin-6
Research Design
Safety
Gene Expression
Drug Therapy
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kim, Han Sang ; Kwon, Hyeong Ju ; Jung, Inkyung ; Yun, Mi Ran ; Ahn, Myung Ju ; Kang, Byung Woog ; Sun, Jong Mu ; Kim, Sung Bae ; Yoon, Dok Hyun ; Park, Keon Uk ; Lee, Se Hoon ; Koh, Yoon Woo ; Kim, Se Hun ; Choi, Eun Chang ; Koo, Dong Hoe ; Sohn, Jin Hee ; Kim, Bomi ; Kwon, Nak Jung ; Yun, Hwan Jung ; Lee, Min Goo ; Lee, Ji Hyun ; Kim, Tae Min ; Kim, Hye Ryun ; Kim, Joo Hang ; Paik, Soonmyung ; Cho, Byoung Chul. / Phase II clinical and exploratory biomarker study of dacomitinib in patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. In: Clinical Cancer Research. 2015 ; Vol. 21, No. 3. pp. 544-552.
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abstract = "Purpose: The goals of this study were to investigate the clinical activity, safety, and biomarkers of dacomitinib, an irreversible tyrosine kinase inhibitor of EGFR, HER2, and HER4, in recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN). Experimental Design: Patients were eligible if the diseases were not amenable to curative treatment and had progressed on platinum-based chemotherapy, and were treated with dacomitinib 45 mg/day. The primary endpoint was objective response rate by RECISTv1.1. Exploratory analysis included the characterization of somatic mutation, gene copy number, gene expression, p16INK4A expression by IHC, and investigation of their relationship with clinical outcomes. Results: Forty-eight patients were evaluable for efficacy and toxicity. Ten patients (20.8{\%}) had partial responses and 31 patients (65{\%}) had stable diseases. The median progressionfree survival (PFS) and overall survival (OS) were 3.9 months [95{\%} confidence interval (CI), 2.9-5.0] and 6.6 months (95{\%} CI, 5.4-10.3). Adverse events were mostly grade 1-2. Mutations in the PI3K pathway (PIK3CA, PTEN ) and high expression of inflammatory cytokines (IL6, IL8, IL1A, IL1B, IL4, and TNF) were significantly associated with shorter PFS (2.9 vs. 4.9 months without mutations, P = 0.013; 2.8 vs. 9.9 months with low expression, P = 0.004). Those harboring PI3K pathway mutations or high inflammatory cytokine expression had shorter median OS (6.1 vs. 12.5 months lacking PI3K pathway mutations and with low inflammatory cytokine expression, P = 0.005). Conclusions: Dacomitinib demonstrated clinical efficacy with manageable toxicity in platinum-failed R/M-SCCHN patients. Screening of PI3K pathway mutation and inflammatory cytokine expression may help identify which R/M-SCCHN patients are likely to gain benefit from dacomitinib.",
author = "Kim, {Han Sang} and Kwon, {Hyeong Ju} and Inkyung Jung and Yun, {Mi Ran} and Ahn, {Myung Ju} and Kang, {Byung Woog} and Sun, {Jong Mu} and Kim, {Sung Bae} and Yoon, {Dok Hyun} and Park, {Keon Uk} and Lee, {Se Hoon} and Koh, {Yoon Woo} and Kim, {Se Hun} and Choi, {Eun Chang} and Koo, {Dong Hoe} and Sohn, {Jin Hee} and Bomi Kim and Kwon, {Nak Jung} and Yun, {Hwan Jung} and Lee, {Min Goo} and Lee, {Ji Hyun} and Kim, {Tae Min} and Kim, {Hye Ryun} and Kim, {Joo Hang} and Soonmyung Paik and Cho, {Byoung Chul}",
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Kim, HS, Kwon, HJ, Jung, I, Yun, MR, Ahn, MJ, Kang, BW, Sun, JM, Kim, SB, Yoon, DH, Park, KU, Lee, SH, Koh, YW, Kim, SH, Choi, EC, Koo, DH, Sohn, JH, Kim, B, Kwon, NJ, Yun, HJ, Lee, MG, Lee, JH, Kim, TM, Kim, HR, Kim, JH, Paik, S & Cho, BC 2015, 'Phase II clinical and exploratory biomarker study of dacomitinib in patients with recurrent and/or metastatic squamous cell carcinoma of head and neck', Clinical Cancer Research, vol. 21, no. 3, pp. 544-552. https://doi.org/10.1158/1078-0432.CCR-14-1756

Phase II clinical and exploratory biomarker study of dacomitinib in patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. / Kim, Han Sang; Kwon, Hyeong Ju; Jung, Inkyung; Yun, Mi Ran; Ahn, Myung Ju; Kang, Byung Woog; Sun, Jong Mu; Kim, Sung Bae; Yoon, Dok Hyun; Park, Keon Uk; Lee, Se Hoon; Koh, Yoon Woo; Kim, Se Hun; Choi, Eun Chang; Koo, Dong Hoe; Sohn, Jin Hee; Kim, Bomi; Kwon, Nak Jung; Yun, Hwan Jung; Lee, Min Goo; Lee, Ji Hyun; Kim, Tae Min; Kim, Hye Ryun; Kim, Joo Hang; Paik, Soonmyung; Cho, Byoung Chul.

In: Clinical Cancer Research, Vol. 21, No. 3, 01.02.2015, p. 544-552.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II clinical and exploratory biomarker study of dacomitinib in patients with recurrent and/or metastatic squamous cell carcinoma of head and neck

AU - Kim, Han Sang

AU - Kwon, Hyeong Ju

AU - Jung, Inkyung

AU - Yun, Mi Ran

AU - Ahn, Myung Ju

AU - Kang, Byung Woog

AU - Sun, Jong Mu

AU - Kim, Sung Bae

AU - Yoon, Dok Hyun

AU - Park, Keon Uk

AU - Lee, Se Hoon

AU - Koh, Yoon Woo

AU - Kim, Se Hun

AU - Choi, Eun Chang

AU - Koo, Dong Hoe

AU - Sohn, Jin Hee

AU - Kim, Bomi

AU - Kwon, Nak Jung

AU - Yun, Hwan Jung

AU - Lee, Min Goo

AU - Lee, Ji Hyun

AU - Kim, Tae Min

AU - Kim, Hye Ryun

AU - Kim, Joo Hang

AU - Paik, Soonmyung

AU - Cho, Byoung Chul

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Purpose: The goals of this study were to investigate the clinical activity, safety, and biomarkers of dacomitinib, an irreversible tyrosine kinase inhibitor of EGFR, HER2, and HER4, in recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN). Experimental Design: Patients were eligible if the diseases were not amenable to curative treatment and had progressed on platinum-based chemotherapy, and were treated with dacomitinib 45 mg/day. The primary endpoint was objective response rate by RECISTv1.1. Exploratory analysis included the characterization of somatic mutation, gene copy number, gene expression, p16INK4A expression by IHC, and investigation of their relationship with clinical outcomes. Results: Forty-eight patients were evaluable for efficacy and toxicity. Ten patients (20.8%) had partial responses and 31 patients (65%) had stable diseases. The median progressionfree survival (PFS) and overall survival (OS) were 3.9 months [95% confidence interval (CI), 2.9-5.0] and 6.6 months (95% CI, 5.4-10.3). Adverse events were mostly grade 1-2. Mutations in the PI3K pathway (PIK3CA, PTEN ) and high expression of inflammatory cytokines (IL6, IL8, IL1A, IL1B, IL4, and TNF) were significantly associated with shorter PFS (2.9 vs. 4.9 months without mutations, P = 0.013; 2.8 vs. 9.9 months with low expression, P = 0.004). Those harboring PI3K pathway mutations or high inflammatory cytokine expression had shorter median OS (6.1 vs. 12.5 months lacking PI3K pathway mutations and with low inflammatory cytokine expression, P = 0.005). Conclusions: Dacomitinib demonstrated clinical efficacy with manageable toxicity in platinum-failed R/M-SCCHN patients. Screening of PI3K pathway mutation and inflammatory cytokine expression may help identify which R/M-SCCHN patients are likely to gain benefit from dacomitinib.

AB - Purpose: The goals of this study were to investigate the clinical activity, safety, and biomarkers of dacomitinib, an irreversible tyrosine kinase inhibitor of EGFR, HER2, and HER4, in recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN). Experimental Design: Patients were eligible if the diseases were not amenable to curative treatment and had progressed on platinum-based chemotherapy, and were treated with dacomitinib 45 mg/day. The primary endpoint was objective response rate by RECISTv1.1. Exploratory analysis included the characterization of somatic mutation, gene copy number, gene expression, p16INK4A expression by IHC, and investigation of their relationship with clinical outcomes. Results: Forty-eight patients were evaluable for efficacy and toxicity. Ten patients (20.8%) had partial responses and 31 patients (65%) had stable diseases. The median progressionfree survival (PFS) and overall survival (OS) were 3.9 months [95% confidence interval (CI), 2.9-5.0] and 6.6 months (95% CI, 5.4-10.3). Adverse events were mostly grade 1-2. Mutations in the PI3K pathway (PIK3CA, PTEN ) and high expression of inflammatory cytokines (IL6, IL8, IL1A, IL1B, IL4, and TNF) were significantly associated with shorter PFS (2.9 vs. 4.9 months without mutations, P = 0.013; 2.8 vs. 9.9 months with low expression, P = 0.004). Those harboring PI3K pathway mutations or high inflammatory cytokine expression had shorter median OS (6.1 vs. 12.5 months lacking PI3K pathway mutations and with low inflammatory cytokine expression, P = 0.005). Conclusions: Dacomitinib demonstrated clinical efficacy with manageable toxicity in platinum-failed R/M-SCCHN patients. Screening of PI3K pathway mutation and inflammatory cytokine expression may help identify which R/M-SCCHN patients are likely to gain benefit from dacomitinib.

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