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Phase II clinical and exploratory biomarker study of dacomitinib in recurrent and/or metastatic esophageal squamous cell carcinoma

The purpose of this study was to investigate the clinical activity, safety and predictive biomarkers of dacomitinib, an irreversible pan-HER inhibitor, in patients with recurrent or metastatic esophageal squamous cell carcinoma (R/M-ESCC). Patients, whose diseases were not amenable to curative treat...

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Autores principales: Kim, Hyo Song, Kim, Sung-Moo, Kim, Hyunki, Pyo, Kyoung-Ho, Sun, Jong-Mu, Ahn, Myung-Ju, Park, Keunchil, Keam, Bhumsuk, Kwon, Nak-Jung, Yun, Hwan Jung, Kim, Hoon-Gu, Chung, Ik-Joo, Lee, Jong Seok, Lee, Kyung Hee, Kim, Dae Joon, Lee, Chang-Geol, Hur, Jin, Chung, Hyunsoo, Park, Jun Chul, Shin, Sung Kwan, Lee, Sang Kil, Kim, Hye Ryun, Moon, Yong Wha, Lee, Yong Chan, Kim, Joo Hang, Paik, Soonmyung, Cho, Byoung Chul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792605/
https://www.ncbi.nlm.nih.gov/pubmed/26462025
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author Kim, Hyo Song
Kim, Sung-Moo
Kim, Hyunki
Pyo, Kyoung-Ho
Sun, Jong-Mu
Ahn, Myung-Ju
Park, Keunchil
Keam, Bhumsuk
Kwon, Nak-Jung
Yun, Hwan Jung
Kim, Hoon-Gu
Chung, Ik-Joo
Lee, Jong Seok
Lee, Kyung Hee
Kim, Dae Joon
Lee, Chang-Geol
Hur, Jin
Chung, Hyunsoo
Park, Jun Chul
Shin, Sung Kwan
Lee, Sang Kil
Kim, Hye Ryun
Moon, Yong Wha
Lee, Yong Chan
Kim, Joo Hang
Paik, Soonmyung
Cho, Byoung Chul
author_facet Kim, Hyo Song
Kim, Sung-Moo
Kim, Hyunki
Pyo, Kyoung-Ho
Sun, Jong-Mu
Ahn, Myung-Ju
Park, Keunchil
Keam, Bhumsuk
Kwon, Nak-Jung
Yun, Hwan Jung
Kim, Hoon-Gu
Chung, Ik-Joo
Lee, Jong Seok
Lee, Kyung Hee
Kim, Dae Joon
Lee, Chang-Geol
Hur, Jin
Chung, Hyunsoo
Park, Jun Chul
Shin, Sung Kwan
Lee, Sang Kil
Kim, Hye Ryun
Moon, Yong Wha
Lee, Yong Chan
Kim, Joo Hang
Paik, Soonmyung
Cho, Byoung Chul
author_sort Kim, Hyo Song
collection PubMed
description The purpose of this study was to investigate the clinical activity, safety and predictive biomarkers of dacomitinib, an irreversible pan-HER inhibitor, in patients with recurrent or metastatic esophageal squamous cell carcinoma (R/M-ESCC). Patients, whose diseases were not amenable to curative treatment and had progressed on platinum-based chemotherapy, were treated with dacomitinib 45mg/day. The primary endpoint was objective response rate by RECISTv 1.1. Predictive biomarker analyses included the characterization of somatic mutations and gene expression using the Ion Torrent AmpliSeq Cancer Hotspot Panel and Nanostring nCounter, and investigation of their relationship with clinical outcomes. Of the 48 evaluable patients, 6 (12.5%) achieved partial responses and 29 (60.4%) had stable disease. The median response duration was 7.1 months. The median progression free survival (PFS) and overall survival (OS) was 3.3 months (95% CI, 2.4-4.3 months) and 6.4 months (95% CI, 4.4-8.4 months). Adverse events were mostly grade 1-2. Gene set enrichment analysis revealed that ERBB signaling pathway is significantly enriched in patients with PFS ≥4 months (n = 12) than PFS < 4 months (n = 21) (p < 0.001). Upregulation of ERBB signaling pathway was significantly associated with longer PFS (5.0 vs. 2.9 months, P = 0.016) and OS (10.0 vs. 4.8 months, P = 0.022). The most frequent mutations were TP53 (61%) followed by CDKN2A (8%), MLH1 (8%), FLT3 (8%) and EGFR (8%). Dacomitinib demonstrated clinical efficacy with manageable toxicity in platinum-failed R/M-ESCC. Screening of ERBB pathway-related gene expression profiles may help identify patients who are most likely benefit from dacomitinib.
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spelling pubmed-47926052016-03-29 Phase II clinical and exploratory biomarker study of dacomitinib in recurrent and/or metastatic esophageal squamous cell carcinoma Kim, Hyo Song Kim, Sung-Moo Kim, Hyunki Pyo, Kyoung-Ho Sun, Jong-Mu Ahn, Myung-Ju Park, Keunchil Keam, Bhumsuk Kwon, Nak-Jung Yun, Hwan Jung Kim, Hoon-Gu Chung, Ik-Joo Lee, Jong Seok Lee, Kyung Hee Kim, Dae Joon Lee, Chang-Geol Hur, Jin Chung, Hyunsoo Park, Jun Chul Shin, Sung Kwan Lee, Sang Kil Kim, Hye Ryun Moon, Yong Wha Lee, Yong Chan Kim, Joo Hang Paik, Soonmyung Cho, Byoung Chul Oncotarget Clinical Research Paper The purpose of this study was to investigate the clinical activity, safety and predictive biomarkers of dacomitinib, an irreversible pan-HER inhibitor, in patients with recurrent or metastatic esophageal squamous cell carcinoma (R/M-ESCC). Patients, whose diseases were not amenable to curative treatment and had progressed on platinum-based chemotherapy, were treated with dacomitinib 45mg/day. The primary endpoint was objective response rate by RECISTv 1.1. Predictive biomarker analyses included the characterization of somatic mutations and gene expression using the Ion Torrent AmpliSeq Cancer Hotspot Panel and Nanostring nCounter, and investigation of their relationship with clinical outcomes. Of the 48 evaluable patients, 6 (12.5%) achieved partial responses and 29 (60.4%) had stable disease. The median response duration was 7.1 months. The median progression free survival (PFS) and overall survival (OS) was 3.3 months (95% CI, 2.4-4.3 months) and 6.4 months (95% CI, 4.4-8.4 months). Adverse events were mostly grade 1-2. Gene set enrichment analysis revealed that ERBB signaling pathway is significantly enriched in patients with PFS ≥4 months (n = 12) than PFS < 4 months (n = 21) (p < 0.001). Upregulation of ERBB signaling pathway was significantly associated with longer PFS (5.0 vs. 2.9 months, P = 0.016) and OS (10.0 vs. 4.8 months, P = 0.022). The most frequent mutations were TP53 (61%) followed by CDKN2A (8%), MLH1 (8%), FLT3 (8%) and EGFR (8%). Dacomitinib demonstrated clinical efficacy with manageable toxicity in platinum-failed R/M-ESCC. Screening of ERBB pathway-related gene expression profiles may help identify patients who are most likely benefit from dacomitinib. Impact Journals LLC 2015-10-09 /pmc/articles/PMC4792605/ /pubmed/26462025 Text en Copyright: © 2015 Kim et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Clinical Research Paper
Kim, Hyo Song
Kim, Sung-Moo
Kim, Hyunki
Pyo, Kyoung-Ho
Sun, Jong-Mu
Ahn, Myung-Ju
Park, Keunchil
Keam, Bhumsuk
Kwon, Nak-Jung
Yun, Hwan Jung
Kim, Hoon-Gu
Chung, Ik-Joo
Lee, Jong Seok
Lee, Kyung Hee
Kim, Dae Joon
Lee, Chang-Geol
Hur, Jin
Chung, Hyunsoo
Park, Jun Chul
Shin, Sung Kwan
Lee, Sang Kil
Kim, Hye Ryun
Moon, Yong Wha
Lee, Yong Chan
Kim, Joo Hang
Paik, Soonmyung
Cho, Byoung Chul
Phase II clinical and exploratory biomarker study of dacomitinib in recurrent and/or metastatic esophageal squamous cell carcinoma
title Phase II clinical and exploratory biomarker study of dacomitinib in recurrent and/or metastatic esophageal squamous cell carcinoma
title_full Phase II clinical and exploratory biomarker study of dacomitinib in recurrent and/or metastatic esophageal squamous cell carcinoma
title_fullStr Phase II clinical and exploratory biomarker study of dacomitinib in recurrent and/or metastatic esophageal squamous cell carcinoma
title_full_unstemmed Phase II clinical and exploratory biomarker study of dacomitinib in recurrent and/or metastatic esophageal squamous cell carcinoma
title_short Phase II clinical and exploratory biomarker study of dacomitinib in recurrent and/or metastatic esophageal squamous cell carcinoma
title_sort phase ii clinical and exploratory biomarker study of dacomitinib in recurrent and/or metastatic esophageal squamous cell carcinoma
topic Clinical Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792605/
https://www.ncbi.nlm.nih.gov/pubmed/26462025
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