Memorial Sloan Kettering Cancer Center, New York, NY;
Andrea Cercek , Kimmie Ng , John H Strickler , Salvatore Siena , Thierry Andre , Eric Van Cutsem , Christina Wu , Andrew Scott Paulson , Joleen M. Hubbard , Andrew L. Coveler , Christos Fountzilas , Adel Kardosh , Pashtoon Murtaza Kasi , Heinz-Josef Lenz , Kristen Keon Ciombor , Elena Elez , Michael Stecher , Pauline Cronin , Wentao Feng , Tanios S. Bekaii-Saab
Background: HER2 overexpression/amplification (HER2+) occurs in 3%-5% of patients (pts) w/ metastatic colorectal cancer (mCRC). Rates of HER2+ can increase to ~10% in pts w/ RAS/BRAF wild-type mCRC tumors. The MOUNTAINEER trial (NCT03043313) evaluated the efficacy and safety of the investigational combination of tucatinib with trastuzumab in pts with HER2+ and RAS wild-type mCRC. Established regional guidelines for mCRC recommend HER2 testing and HER2-directed treatment options; however, there is currently no established best practice for HER2 testing and interpretation in mCRC. Here, we present data from a concordance analysis comparing breast and gastric HER2 testing algorithms in the mCRC setting. Methods: The MOUNTAINEER trial enrolled pts w/ HER2+ mCRC identified using ≥1 method: tissue-based local immunohistochemistry (IHC), in situ hybridization (ISH), and/or next-generation sequencing (NGS) testing. Archival or fresh tumor tissue was submitted to a sponsor-designated central laboratory for confirmatory HER2 testing w/ IHC/FISH per the package insert of the FDA approved assay and scored by both the breast and gastric algorithms for HER2 IHC. A positive result per the breast scoring criteria for IHC requires circumferential membrane staining for HER2, while the gastric criteria allows for circumferential, basolateral, or lateral staining patterns. Results: A total of 114 pts were enrolled with HER2+ tumors per ≥1 local testing methods; 69 pts were HER2+ by NGS, 46 by IHC 3+, and 36 by ISH. Of 105 pts who had tissue available for central HER2 testing w/IHC/FISH, 98 had valid HER2 results; 82/98 (83.7%) of pts had tumors centrally confirmed as HER2+ using both the breast and gastric algorithms. Tissue samples from pts in the MOUNTAINEER trial had 100% concordance between breast and gastric algorithms in HER2 status and 99% concordance in HER2 IHC score. Conclusions: Central pathology testing using both the breast and gastric criteria showed high concordance between these two commonly used algorithms. A high central confirmation rate of local HER2+ results was also observed. These data support the use of either the breast or gastric algorithms to identify HER2+ mCRC tumors until an FDA-approved HER2 assay is available for mCRC. Clinical trial information: NCT03043313.
Gastric Algorithm (N=105) | |||
---|---|---|---|
Breast Algorithm (N=105) | Negative | Positive | Not Determined |
Negative | 16 | 0 | 0 |
Positive | 0 | 82 | 0 |
Not Determined | 0 | 0 | 7 |
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Disclosures
First Author: Nicholas Patrick McAndrew
2023 ASCO Annual Meeting
First Author: Tarek Mohamed Ahmed Abdel-Fatah
2024 ASCO Genitourinary Cancers Symposium
First Author: David H Aggen
2023 ASCO Gastrointestinal Cancers Symposium
First Author: Tanios S. Bekaii-Saab