TY - JOUR
T1 - Upfront molecular testing in patients with advanced gastro-esophageal cancer
T2 - Is it time yet?
AU - Mikhail, Sameh
AU - Ciombor, Kristen
AU - Noonan, Anne
AU - Wu, Christina
AU - Goldberg, Richard
AU - Zhao, Weiqiang
AU - Wei, Lai
AU - Mathey, Kristina
AU - Yereb, Melissa
AU - Timmers, Cynthia
AU - Bekaii-Saab, Tanios
PY - 2015
Y1 - 2015
N2 - Introduction: Targeting HER2 has improved outcomes in metastatic GE (mGE) cancer. In this study, we aim to explore the feasibility of molecular profiling in patients with refractory mGE cancer in routine clinical practice. Methods: Archival formalin-fixed, paraffin-embedded (FFPE) samples for patients with mGE were analyzed with commercially available targeted next generation sequencing (NGS) and/or FISH for MET amplification. We also reviewed the patients' medical records for concurrent HER 2 testing. Results: Tumor samples from 99 patients with mGE cancer were analyzed as follows: NGS (N = 56), FISH for MET amplification (N = 65), IHC and/or FISH for HER2 (N = 87). Of patients who underwent NGS, 50/56 (89%) had at least one actionable molecular alteration. The most notable actionable alterations included cell cycle abnormalities (58%), HER2 amplification (30%), PI3KCA mutation (14%), MCL1 amplification (11%), PTEN loss (9%), CDH1 mutation (2%) and MET amplification (5%). Ninety-two percent (12/13) of patients with HER2 amplification by NGS were positive for HER2 by IHC and/or FISH. In contrast, only 12/18 (66%) patients positive for HER2 by IHC and/or FISH demonstrated HER2 amplification by NGS. Conclusion: Comprehensive molecular testing is feasible in clinical practice and provides a platform for screening patients for molecularly guided clinical trials and available targeted therapies.
AB - Introduction: Targeting HER2 has improved outcomes in metastatic GE (mGE) cancer. In this study, we aim to explore the feasibility of molecular profiling in patients with refractory mGE cancer in routine clinical practice. Methods: Archival formalin-fixed, paraffin-embedded (FFPE) samples for patients with mGE were analyzed with commercially available targeted next generation sequencing (NGS) and/or FISH for MET amplification. We also reviewed the patients' medical records for concurrent HER 2 testing. Results: Tumor samples from 99 patients with mGE cancer were analyzed as follows: NGS (N = 56), FISH for MET amplification (N = 65), IHC and/or FISH for HER2 (N = 87). Of patients who underwent NGS, 50/56 (89%) had at least one actionable molecular alteration. The most notable actionable alterations included cell cycle abnormalities (58%), HER2 amplification (30%), PI3KCA mutation (14%), MCL1 amplification (11%), PTEN loss (9%), CDH1 mutation (2%) and MET amplification (5%). Ninety-two percent (12/13) of patients with HER2 amplification by NGS were positive for HER2 by IHC and/or FISH. In contrast, only 12/18 (66%) patients positive for HER2 by IHC and/or FISH demonstrated HER2 amplification by NGS. Conclusion: Comprehensive molecular testing is feasible in clinical practice and provides a platform for screening patients for molecularly guided clinical trials and available targeted therapies.
KW - C-MET
KW - Gastro-esophageal cancer
KW - Molecular profiling
KW - Next generation sequencing
KW - Targeted therapy
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U2 - 10.18632/oncotarget.4247
DO - 10.18632/oncotarget.4247
M3 - Article
C2 - 26082439
AN - SCOPUS:84941248892
SN - 1949-2553
VL - 6
SP - 22206
EP - 22213
JO - Oncotarget
JF - Oncotarget
IS - 26
ER -