This program explores treatment options for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic colorectal cancer (mCRC). To make informed decisions when treating patients with HER2-positive status, clinicians must understand using HER2 as a testing target and know the latest treatment options available. This activity raises clinician awareness of the impact of testing for HER2 status in patients with mCRC and of identifying patients with CRC who would benefit from HER2-directed therapies.
What Are the Clinical Features of HER2 Amplified Colorectal Cancers?
What Are the Clinical Features of HER2 Amplified Colorectal Cancers?
Welcome to CME on ReachMD. This episode is part of our MinuteCME curriculum.
Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements as well as the learning objectives.
Hi, my name is Andrea Cercek. I'm a Medical Oncologist and Section Head Colorectal Cancer at Memorial Sloan Kettering Cancer Center. And I'm excited today to discuss the clinical features of HER2 amplified colorectal cancers.
So HER2 as a target in colorectal cancer, it's a receptor tyrosine kinase which is encoded by ERBB2, it has no soluble ligand that we know of, and it heterodimerizes with other ligand-bound HER2 family members. And when HER2 heterodimerizes with HER3, that heterodimer is a potent driver of PI3 kinase signaling. And there are multiple therapies that target HER2 and the HER2 heterodimers. And once they dimerize, they basically turn on and lead to cell growth differentiation and cell survival in cancer cells.
So when we look at HER2 across multiple tumor types, you can see that it's altered in many tumor types. Of course, the breast and gastric are most common and most known and sort of most developed in terms of targeting, but obviously is seen in colon as well. And we have HER2 amplification, overexpression, and then HER2 mutation. And all of those can lead to tumorigenesis. But what we're going to specifically talk about today is HER2 gene amplification as a target.
So HER2 amplification in colorectal cancer. It's about 4%. This is in the metastatic setting. And we believe it's similar in early-stage disease as well. And it's actually enriched in the RAS/RAF wild-type tumors where it ends up being about 10% of all-comers. But it's an important part of the biomarker pie, if you will, in colorectal cancer.
So what do we know about it in terms of clinical characteristics? Many of these tumors most typically are left sided, not exclusively, but the large majority are in the sigmoid or the rectum. There's homogeneous expression of HER2 in colorectal cancer. It's actually not mutually exclusive with RAS or BRAF mutations, which is important to keep in mind, particularly when we think about treatment and targeted treatment with combination of monoclonal antibodies and TKIs. Because the tumors need to be RAS wild-type. So it's always important to check for HER2 amplification as well as RAS mutation in particular. And it is more commonly associated with lung and brain metastases. And I'll show that data in a little bit. And, you know, I have a question mark here for whether or not it's resistant to anti-EGFR antibodies. But we do see this over and over in preclinical models as well as in retrospective analyses of patients that had HER2 amplified RAS wild-type tumors that received anti-EGFR therapy that benefit, which is significantly less than what we're seeing in patients that have RAS wild-type tumors that are left sided and not HER2 amplified.
And this is just some other data to show you. So this was a nice retrospective analysis, looking at patients that received anti-EGFR therapy in the metastatic setting, standard of care, left-sided tumors. And you can clearly see by the graph that the patients that had the HER2 amplified tumors that received the same anti-EGFR therapy did significantly worse in terms of PFS, progression-free survival. So really suggesting that we shouldn't treat this population that's HER2 amplified RAS wild-type with anti-EGFR therapy but rather focus on HER2 targeting.
So looking at the clinical characteristics of HER2 tumors in a little bit more detail, and this was nice work done by the Italian group led by Dr. Sartore-Bianchi. Again just to show you more likely to occur in the rectum, more likely to metastasize to the lungs, and actually more likely to involve multiple metastatic sites. So just something to keep in mind when seeing these patients. Of course, you know, I can't stress enough the importance of next generation sequencing in all-comers with metastatic colorectal cancer, looking at that pie, looking at potential biomarkers, but particularly for HER2 amplified RAS wild-type patients in terms of treatment options, as we now have FDA approval in third-line for HER2 amplified RAS wild-type tumors with tucatinib and trastuzumab, something to keep in mind when seeing these patients if you meet them later on in therapy and they'd have not yet had next generation sequencing or specifically HER2 amplification.
You have been listening to CME on ReachMD. This activity is jointly provided by Global Learning Collaborative (GLC) and TotalCME, Inc. and is part of our MinuteCME curriculum.
To receive your free CME credit, or to download this activity, go to ReachMD.com/CME. Thank you for listening.
This activity has been designed to meet the educational needs of the interprofessional team, including community oncologists, oncology nurses, pathologists, gastroenterologists, as well as other clinicians involved in the management of patients with colorectal cancer.
After participating in this educational activity, participants should be better able to:
- Apply appropriate diagnostic methods to identify patients with mCRC who are candidates for HER2-directed therapy
- Differentiate between HER2-targeted tyrosine kinase inhibitors based on downstream effects of target specificity
- Evaluate efficacy and safety of current treatment options to inform treatment strategies for patients with HER2-positive mCRC
- Utilize understanding of target profiles, efficacy, and safety considerations to select optimal HER2-targeted TKI combination regimens for a patient with HER2-positive mCRC
In support of improving patient care, this activity has been planned and implemented by Global Learning Collaborative (GLC) and TotalCME, Inc. GLC is jointly accredited by the American Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE) and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team.
This activity was planned by and for the healthcare team, and learners will receive 1.0 Interprofessional Continuing Education (IPCE) credit(s) for learning and change.
In accordance with the ACCME Standards for Integrity and Independence, Global Learning Collaborative (GLC) requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any ineligible company. GLC mitigates all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all educational programs.
The following faculty have disclosed:
John H. Strickler, MD, faculty for this educational event, is a contracted researcher for Abbvie, Amgen, AStar D3, Bayer, Curegenix, Daiichi-Sankyo, Eli Lilly, Erasca, Gossamer Bio, Leap Therapeutics, Nektar, Roche/ Genentech, Sanofi, Seagen, and Silverback Therapeutics; and receives consulting fees from Abbvie, Amgen, AstraZeneca, Bayer, Beigene, Daiichi-Sankyo, Eli Lilly, GSK, Natera, Pfizer, Pionyr Immunotherapeutics, Seagen, Silverback Therapeutics, Takeda, and Viatris.
Andrea Cercek, MD, faculty for this educational event, is a contracted researcher for GSK, and Seagen; currently has patents pending for HAI FUDR in DPD deficiency and Neoadjuvant PD1 in locally adv dMMR solid tumors; and receives consulting fees from Seagen, Merck, Bayer, GSK, and Pfizer.
The following planners/reviewers/managers have disclosed:
Megan Reimann, PharmD, BCOP, planner for this educational event, has no relevant financial relationships with ineligible companies.
William Mencia, MD, FACEHP, CHCP, reviewer for this educational event, has no relevant financial relationships with ineligible companies.
TotalCME, Inc. planners and managers have no relevant commercial relationships to disclose.
All the relevant financial relationships for these individuals have been mitigated.
The views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of GLC and TotalCME, Inc. This presentation is not intended to define an exclusive course of patient management; the participant should use his/her clinical judgment, knowledge, experience, and diagnostic skills in applying or adopting for professional use any of the information provided herein. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient's conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Links to other sites may be provided as additional sources of information. Once you elect to link to a site outside of MedEd On The Go you are subject to the terms and conditions of use, including copyright and licensing restrictions, of that site.
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This activity is supported by an independent educational grant from Seagen.
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