Upfront molecular testing in patients with advanced gastro-esophageal cancer: Is it time yet?
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Sameh Mikhail1, Kristen Ciombor1, Anne Noonan1, Christina Wu1, Richard Goldberg1, Weiqiang Zhao2, Lai Wei3, Kristina Mathey1, Melissa Yereb1, Cynthia Timmers1, Tanios Bekaii-Saab1
1Department of Medicine, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio 43221, USA
2Department of Pathology, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio 43221, USA
3Department of Biostatistics, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio 43221, USA
Sameh Mikhail, e-mail: [email protected]
Keywords: next generation sequencing, gastro-esophageal cancer, molecular profiling, c-MET, targeted therapy
Received: March 17, 2015 Accepted: May 29, 2015 Published: June 10, 2015
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.
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