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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 Lee  ;  Ji Hyun Lee  ;  Tae-Min Kim  ;  Hye Ryun Kim  ;  Joo Hang Kim  ;  Soonmyung Paik  ;  Byoung Chul Cho 
 CLINICAL CANCER RESEARCH, Vol.21(3) : 544-552, 2015 
Journal Title
Issue Date
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use* ; Biomarkers ; Carcinoma, Squamous Cell/drug therapy* ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/mortality ; Carcinoma, Squamous Cell/pathology* ; Cluster Analysis ; Female ; Gene Dosage ; Gene Expression Profiling ; Head and Neck Neoplasms/drug therapy* ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/mortality ; Head and Neck Neoplasms/pathology* ; Humans ; Male ; Middle Aged ; Mutation ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Prognosis ; Protein Kinase Inhibitors/administration & dosage ; Protein Kinase Inhibitors/adverse effects ; Protein Kinase Inhibitors/therapeutic use* ; Quinazolinones/administration & dosage ; Quinazolinones/adverse effects ; Quinazolinones/therapeutic use* ; Retreatment ; Risk Factors ; Treatment Outcome
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, p16(INK4A) 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 progression-free 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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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Kho, Yoon Woo(고윤우)
Kwon, Hyeong Ju(권형주)
Kim, Joo Hang(김주항)
Kim, Han Sang(김한상) ORCID logo https://orcid.org/0000-0002-6504-9927
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Paik, Soon Myung(백순명) ORCID logo https://orcid.org/0000-0001-9688-6480
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Lee, Ji Hyun(이지현)
Jung, Inkyung(정인경) ORCID logo https://orcid.org/0000-0003-3780-3213
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Choi, Eun Chang(최은창)
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