KEY TAKEAWAYS
- The MOUNTAINEER trial evaluated the efficacy and safety of the investigational combination of tucatinib with trastuzumab in patients with HER2+ and RAS wild-type metastatic colorectal cancer.
- HER2 overexpression/amplification occurs in 3%-5% of patients with metastatic colorectal cancer, and rates can increase to ~10% in patients with RAS/BRAF wild-type mCRC tumors.
- Established regional guidelines recommend HER2 testing and HER2-directed treatment options, but there is currently no established best practice for HER2 testing and interpretation in mCRC.
- A total of 114 patients were enrolled with HER2+ tumors per local testing methods, and 82/98 (83.7%) of patients had tumors centrally confirmed as HER2+ using both the breast and gastric algorithms.
- 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.
Just 3–5% of patients (pts) with metastatic colorectal cancer have HER2 overexpression/amplification (HER2+) (mCRC). Patients with RAS/BRAF wild-type mCRC tumours have been shown to have HER2+ rates as high as 10%. Patients with HER2+ and RAS wild-type mCRC were included in the MOUNTAINEER study (NCT03043313) to assess the effectiveness and safety of the experimental combination of tucatinib plus trastuzumab. Although HER2 testing and HER2-directed treatment options are recommended by established regional guidelines for mCRC, there is still no defined best practice for HER2 testing and interpretation in mCRC. We show results from a concordance analysis comparing the HER2 testing algorithms for breast and stomach cancers in the context of mCRC.
Patients with HER2+ mCRC diagnosed by tissue-based local immunohistochemistry (IHC), in situ hybridization (ISH), or next-generation sequencing (NGS) testing were eligible to participate in the MOUNTAINEER study. For confirmatory HER2 testing with IHC/FISH, either archived or fresh tumour tissue was sent to a sponsor-designated central laboratory, where it was scored using the breast and gastric algorithms for HER2 IHC, as described in the package insert for the FDA-approved assay. Breast IHC scoring standards necessitate HER2 membrane staining that is circumferential, but stomach criteria are flexible enough to accommodate basolateral or lateral staining.
Over 114 patients (pts) with HER2+ tumours as determined by at least one local test were included; 69 pts were HER2+ by NGS, 46 pts were HER2+ by IHC 3+, and 36 pts were HER2+ by ISH. 82 out of 98 (83.7%) patients had tumours centrally validated as HER2+ using both the breast and gastric algorithms. Among the 105 patients for whom tissue was available for central HER2 testing with IHC/FISH, 98 had valid HER2 results. Among patients participating in the MOUNTAINEER study, there was a perfect match between breast and gastric algorithms for HER2 status and a 99% match for HER2 IHC score.
Breast and stomach criteria were tested in a central laboratory setting, and the results demonstrated a high degree of agreement between the two regularly used algorithms. There was also a significant rate of HER2+ results being confirmed at the central lab. These results lend credence to the idea that, in the absence of an FDA-approved HER2 assay for mCRC, either the breast or gastric algorithms might be used to detect HER2+ cancers.
Source: https://meetings.asco.org/abstracts-presentations/216041
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT03043313
Cercek, A., Ng, K., Strickler, J.H., Siena, S., Andre, T., Van Cutsem, E., Wu, C., Paulson, A.S., Hubbard, J.M., Coveler, A.L., Fountzilas, C., Kardosh, A., Kasi, P.M., Lenz, H.-J., Ciombor, K.K., Elez, E., Stecher, M., Cronin, P., Feng, W. and Bekaii-Saab, T.S. (2023). HER2 testing in colorectal cancer: Concordance analysis between breast and gastric scoring algorithms from the MOUNTAINEER trial. Journal of Clinical Oncology, 41(4_suppl), pp.198–198. doi:https://doi.org/10.1200/jco.2023.41.4_suppl.198.
