International harmonization of diagnostic criteria for HER2-amplified metastatic colorectal cancer and application of targeted next-generation sequencing panel as a diagnostic method.

Authors

null

Satoshi Fujii

National Cancer Center, EPOC, Chiba, Japan

Satoshi Fujii , Anthony Martin Magliocco , Emanuele Valtorta , Jihun Kim , Wataru Okamoto , Jeong Eun Kim , Kentaro Sawada , Yoshiaki Nakamura , Valter Torri , Scott Kopetz , Woong Yang Park , Katsuya Tsuchihara , Tae Won Kim , Kanwal Pratap Singh Raghav , Salvatore Siena , Takayuki Yoshino

Organizations

National Cancer Center, EPOC, Chiba, Japan, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, Division of Pathology, Department of Laboratory Medicine, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy, Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, National Cancer Center, Kashiwa, Japan, Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, Seoul, Korea, Republic of (South), National Cancer Center Hospital East, Kashiwa, Japan, Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan, Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy, Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, Samsung Genome Institute, Samsung Medical Center, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, Division of Translational Research, Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba, Japan, Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of (South), Dipartimento di Oncologia ed Emato-Oncologia, niversità degli Studi di Milano, Milano, Italy

Research Funding

Other Foundation

Background: HER2 amplification (HER2+) in metastatic colorectal cancer (mCRC) is associated with resistance to anti-EGFR antibodies and response to HER2 targeted therapies. This study assessed the diagnostic criteria on HER2+ mCRC among four groups (GI-SCREEN-Japan, SWOG-USA, HERACLES-Italy, and Korea) and harmonized the criteria for patient enrollment in clinical trials that target these patients (pts). Methods: Samples from 475 and 16 pts with mCRC were used in exploratory and validation cohorts, respectively. We assessed HER2 status by immunohistochemistry (IHC) and HER2/CEP17 ratio and gene copy number (GCN) by fluorescence in situ hybridization (FISH) and copy number variations (CNV) by targeted next-generation sequencing (NGS) panel. OCA by ThemoFisher and AMC v3 by illumina were used in exploratory and validation cohorts, respectively for the cross-validation of NGS panels. Results: The consensus diagnostic criteria for HER2+ mCRC was reached; IHC 3+ or IHC 2+ and HER2/CEP17 ratio by FISH ≥ 2.0, and tumor content > 10% for surgically resected specimens (separate quantity criteria were established for biopsy specimens). The median GCN and CNV for pts who met consensus criteria for HER2+ was 10.9 and 27.7 compared to 2.5 (P< 0.0001) and 3.5 (P< 0.0001), respectively in pts who were HER2-. These findings were validated in validation cohort (GCN: 16.2 v 2.4, P= 0.0002; CNV: 42.5 v 2.0, P= 0.0003). GCN also showed strong correlation with CNV in both cohorts (r: exploratory: 0.90, validation: 0.97; P< 0.0001). CNV in cross validation of OCA and AMC v3 also showed strong correlation (r: 0.97, P< 0.0001). The CNV for pts fulfilling the consensus criteria was more than 4.0 in the two cohorts. The accuracy of the IHC/FISH criteria was validated for mCRC pts, providing cross-validation of NGS panels. Conclusions: We were able to verify the HER2 classification consistency between CNV by NGS and IHC/FISH by harmonizing diagnostic criteria for HER2+. This strategy can help establish diagnostic criteria for HER2+ cancer by allowing for different methodologies to be used for pts screening for trial eligibility.

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Abstract Details

Meeting

2018 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gastrointestinal (Colorectal) Cancer

Track

Gastrointestinal Cancer—Colorectal and Anal

Sub Track

Epidemiology/Outcomes

Citation

J Clin Oncol 36, 2018 (suppl; abstr 3594)

DOI

10.1200/JCO.2018.36.15_suppl.3594

Abstract #

3594

Poster Bd #

87

Abstract Disclosures

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