https://scholars.lib.ntu.edu.tw/handle/123456789/629462
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | HSIANG-FONG KAO | en_US |
dc.contributor.author | BIN-CHI LIAO | en_US |
dc.contributor.author | YEN-LIN HUANG | en_US |
dc.contributor.author | HUAI-CHENG HUANG | en_US |
dc.contributor.author | Chun-Nan Chen | en_US |
dc.contributor.author | TSENG-CHENG CHEN | en_US |
dc.contributor.author | Hong, Yuan Jing | en_US |
dc.contributor.author | Chan, Ching Yi | en_US |
dc.contributor.author | JEAN-SAN CHIA | en_US |
dc.contributor.author | RUEY-LONG HONG | en_US |
dc.date.accessioned | 2023-03-21T02:22:54Z | - |
dc.date.available | 2023-03-21T02:22:54Z | - |
dc.date.issued | 2022-04-15 | - |
dc.identifier.issn | 10780432 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/629462 | - |
dc.description.abstract | Purpose: EGFR pathway inhibition may promote anti- programmed cell death protein 1 (PD-1) responses in preclinical models, but how EGFR inhibition affects tumor antigen presentation during anti-PD-1 monotherapy in humans remain unknown. We hypothesized that afatinib, an irreversible EGFR tyrosine kinase inhibitor, would improve outcomes in patients treated with pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) by promoting antigen presentation and immune activation in the tumor microenvironment. Patients and Methods:The ALPHA study (NCT03695510) was a single-arm, Phase II study with Simon's 2-stage design. Afatinib and pembrolizumab were administered to patients with platinum-refractory, recurrent, or metastatic HNSCC. The primary endpoint was the objective response rate (ORR). The study applied gene expression analysis using a NanoString PanCancer Immune Profiling Panel and next-generation sequencing using FoundationOne CDx. Results: From January 2019 to March 2020, the study enrolled 29 eligible patients. Common treatment-related adverse events were skin rash (75.9%), diarrhea (58.6%), and paronychia (44.8%). Twelve patients (41.4%) had an objective partial response to treatment. The median progression-free survival was 4.1 months, and the median overall survival was 8.9 months. In a paired tissue analysis, afatinib- pembrolizumab were found to upregulate genes involved in antigen presentation, immune activation, and natural killer cell-mediated cytotoxicity. Unaltered methylthioadenosine phosphorylase and EGFR amplification may predict the clinical response to the therapy. Conclusions: Afatinib may augment pembrolizumab therapy and improve the ORR in patients with HNSCC. Bioinformatics analysis suggested the enhancement of antigen presentation machinery in the tumor microenvironment. | en_US |
dc.language.iso | en | en_US |
dc.publisher | AMER ASSOC CANCER RESEARCH | en_US |
dc.relation.ispartof | Clinical Cancer Research | en_US |
dc.subject | THERAPY LUX-HEAD; OPEN-LABEL; 2ND-LINE TREATMENT; PD-1 BLOCKADE; IFN-GAMMA; EXPRESSION; CANCER; CHEMOTHERAPY; RESISTANCE; METHOTREXATE | en_US |
dc.title | Afatinib and Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (ALPHA Study): A Phase II Study with Biomarker Analysis | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1158/1078-0432.CCR-21-3025 | - |
dc.identifier.pmid | 35046059 | - |
dc.identifier.scopus | 2-s2.0-85127962142 | - |
dc.identifier.isi | WOS:000789051900001 | - |
dc.identifier.url | https://api.elsevier.com/content/abstract/scopus_id/85127962142 | - |
dc.relation.pages | 1560 | en_US |
dc.relation.journalvolume | 28 | en_US |
dc.relation.journalissue | 8 | en_US |
dc.relation.pageend | 1571 | en_US |
item.fulltext | no fulltext | - |
item.openairetype | journal article | - |
item.languageiso639-1 | en | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
crisitem.author.dept | Oncology-NTUH | - |
crisitem.author.dept | Medical Oncology-NTUCC | - |
crisitem.author.dept | Pathology-NTUCC | - |
crisitem.author.dept | Medical Oncology-NTUCC | - |
crisitem.author.dept | Otolaryngology | - |
crisitem.author.dept | Otolaryngology-NTUH | - |
crisitem.author.dept | Otolaryngology | - |
crisitem.author.dept | Otolaryngology-NTUH | - |
crisitem.author.dept | Clinical Dentistry | - |
crisitem.author.dept | Clinical Medicine | - |
crisitem.author.dept | Oral Biology | - |
crisitem.author.dept | Microbiology | - |
crisitem.author.dept | Dentistry-NTUH | - |
crisitem.author.dept | School of Dentistry | - |
crisitem.author.dept | Oncology | - |
crisitem.author.orcid | 0000-0001-9186-0134 | - |
crisitem.author.orcid | 0000-0002-7092-0764 | - |
crisitem.author.orcid | 0000-0002-2650-3736 | - |
crisitem.author.orcid | 0000-0002-5431-0712 | - |
crisitem.author.orcid | 0000-0001-8100-7914 | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | National Taiwan University Cancer Center (NTUCC) | - |
crisitem.author.parentorg | National Taiwan University Cancer Center (NTUCC) | - |
crisitem.author.parentorg | National Taiwan University Cancer Center (NTUCC) | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
顯示於: | 醫學院附設醫院 (臺大醫院) |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。