Additional Advances in HER2-Positive Metastatic Colorectal Cancer Research and Clinical Trials With Christopher Lieu, MD

Dr. Christopher Lieu, Associate Director of Clinical Research at the University of Colorado Cancer Center and Vice Chair of the National Comprehensive Cancer Network (NCCN), is currently serving as chair of i3 Health’s online activity, live webinar, and meeting series, Hitting the Target in HER2-Positive Metastatic Colorectal Cancer. With numerous research advances occurring in this field during the past year, Dr. Lieu sat down with us again to share updates in targeted therapies for HER2-positive metastatic colorectal cancer and the evolving landscape of biomarkers under investigation for this disease.

Oncology Data Advisor: Hi, everyone. Today, I have the pleasure of being joined by Dr. Christopher Lieu. Dr. Lieu is serving as chair of i3 Health’s online activity and meeting series, Hitting the Target in HER2-Positive Metastatic Colorectal Cancer. With more advances occurring in this field since recording, Dr. Lieu is now sitting down with us again to share some of the research updates from the past year. Thank you so much for coming on the show today.

Christopher Lieu, MD: Oh, thanks so much for having me.

Oncology Data Advisor: To start off, would you like you to introduce yourself and share a little bit about what you do?

Dr. Lieu: Sure, my name is Chris Lieu. I’m a Gastrointestinal (GI) Medical Oncologist here at the University of Colorado Cancer Center, specializing in colorectal cancer. We’re investigating immunotherapy strategies for metastatic colorectal cancer as well as the rising incidence of early-onset colorectal cancer in our young adult population, trying to figure out why that is and how we can treat our patients better.

Oncology Data Advisor: Diving into the conversation, have there been any new advances in HER2-positive metastatic colorectal cancer treatment and management that have occurred since last June when this activity was recorded?

Dr. Lieu: After we recorded the activity for HER2 amplification in colorectal cancer, there was actually some data presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in 2023, looking at the DESTINY-CRC02 study (one of the studies leading to the recent approval of fam-trastuzumab deruxtecan-nxki for HER2-positive solid tumors). In the recording, we talked about DESTINY-CRC01, which looked at trastuzumab deruxtecan in patients with HER2-amplified metastatic colorectal cancer. The 02 study is one that we’ll be talking about in future lectures. In this particular study, they looked at two different doses of trastuzumab deruxtecan, a higher and a lower dose. Outcomes showed that overall survival results were actually fairly similar even with the lower dose of trastuzumab deruxtecan, which obviously has advantages when you’re talking about trying to limit toxicities—giving patients effective therapy, but with as few side effects as possible.

One of the other things that we’re really looking into is the impact of HER2 amplification on the use of anti–epidermal growth factor receptor (EGFR) therapy for patients with metastatic colorectal cancer. There is some data that’s emerged, suggesting that HER2 amplification is a resistance mechanism to our anti-EGFR agents, cetuximab and panitumumab. There has been some recent data looking back at an old trial, CALGB-0405. This looked at chemotherapy with bevacizumab versus chemotherapy with cetuximab in patients with RAS wild-type metastatic colorectal cancer. When they looked back at that population, they did not see a similar association of HER2-mediated resistance against cetuximab. This is a little bit of an evolving field and another thing that practitioners need to keep in mind in terms of selecting anti-EGFR therapy for this highly select group of patients.

Oncology Data Advisor: That’s great to know, and it’s really exciting to hear about all these new updates. Are there any ongoing trials or research in this space that you’re looking forward to seeing results of?

Dr. Lieu: When we look at the impact of anti-HER2 therapy, particularly trastuzumab with tucatinib and trastuzumab deruxtecan in the later-line setting for our patients with metastatic colorectal cancer, a lot of these trials are now moving it up earlier in lines of therapy. The MOUNTAINEER study is looking at chemotherapy in combination with trastuzumab and tucatinib in the frontline setting. These are patients that have previously not been treated for their metastatic colorectal cancer, and these trials are ongoing. I’m not sure when they’re going to report out, but these are some of the trials that are happening currently that we’re looking forward to hearing about in the near future.

Oncology Data Advisor: Looking forward to that as well. Are you currently involved in any CRC research that you’d like to highlight?

Dr. Lieu: A lot of the work that we’re doing here at the University of Colorado is really trying to focus on why immunotherapy doesn’t work for a majority of our patients with microsatellite-stable metastatic colorectal cancer. We’re doing some laboratory work and translational work looking at different combinations of immunotherapy in combination with targeted therapy, and we actually have several investigator-initiated trials investigating whether we can utilize immunotherapy combinations for these patients that traditionally don’t respond to immunotherapy. Again, it’s very, very early, and we’re still in early-phase clinical trials, but we’re just trying to provide some hope for our patients and obviously look for newer combinations to give to our patients with microsatellite-stable metastatic colorectal cancer.

Oncology Data Advisor: Absolutely. With all these new and ongoing advances that you’re mentioning, what are you most looking forward to seeing in the treatment and management of this disease in the coming years?

Dr. Lieu: I think it really does center around investigating some of the things that we can do from an immunotherapy standpoint for our patients. Again, only 4% of our patients are microsatellite instability (MSI)–high, and that’s the patient population that is most likely to respond to immunotherapy. I think what you’ll see really over the next year or so is the use of immunotherapies for patients that do not have liver metastasis. You’re going to see some of these trials come out, particularly in patients that have, say, lung-only metastasis. There’s some suggestion in earlier-phase studies that these patients may actually respond to certain types of immunotherapy or immunotherapy combination strategies. In that patient population, which is fairly sizable still, we’re going to look for data. We’re also starting to see newer immunotherapies like chimeric antigen receptor (CAR) T-cell therapy coming into the clinical trial arena for solid tumors, and colorectal cancer is one of those. Those are some of the things that we’re excited about as well.

Oncology Data Advisor: Awesome, thanks for sharing all of that. My final question for you is, do you have any messages or words of advice for clinicians who treat patients with this disease, especially right now with March being Colorectal Cancer Awareness month?

Dr. Lieu: That’s right. There are two things. Number one, it’s nice that this month is Colorectal Cancer Awareness month because we’re seeing such a rise in early-onset colorectal cancer. Raising awareness will really save lives as well as just inform the public about of what they should be looking for in terms of risk factors and warning signs. The second thing is this program is focused on HER2-amplified metastatic colorectal cancer, but it’s part of a much bigger picture that’s developing in metastatic colorectal cancer, where biomarker analysis is starting to guide therapy for a higher percentage of patients. We certainly, as physicians and providers, want to have more and more targeted therapy options that provide our patients with the opportunity to live longer with their disease, but also live better if they have limited side effects.

The key, really, is we’re talking about HER2 as a biomarker. We’ve got to get this biomarker testing done on every single patient that’s eligible for treatment, and we want to do this early in their treatment so we can start to think about not only what chemotherapies we want to give our patients, but what targeted therapies we might give in subsequent lines of therapy. That’s what a lot of the talk on HER2 is about, but there are new and even more exciting biomarkers on the horizon, and it just really speaks to the importance of this type of testing.

Oncology Data Advisor: Absolutely. As we wrap up, anything else you’d like to mention either about your work in this space or about the activity itself?

Dr. Lieu: I appreciate everyone for being interested in how we test for these biomarkers in colorectal cancer, how we provide these options for our patients, and just making sure that we improve outcomes as much as we can.

Oncology Data Advisor: Amazing. Well, thank you so much for taking the time today to share all these updates. It’s wonderful to learn about, and we’re definitely looking forward to hearing the full presentation and hearing more in the webinars as well. Thank you again for your time.

Dr. Lieu: Thanks so much.

About Dr. Lieu

Christopher Lieu, MD, is an Associate Professor and the Associate Director of Clinical Research at the University of Colorado Cancer Center in Aurora, Colorado. In addition, he is Co-Director of GI Medical Oncology at the University of Colorado Cancer Center, Vice Chair of the National Comprehensive Cancer Network, and Vice Chair of the National Cancer Institute (NCI) Colon Cancer Task Force. Dr. Lieu specializes in the treatment of GI cancers, including colorectal, hepatocellular, esophageal, pancreatic, gastric, bile duct, anal, and gallbladder cancers. His research focuses on developmental therapeutics and resistance mechanisms to targeted therapy in GI cancers.

For More Information

Raghav KPS, Siena S, Takashima A, et al (2023). Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-overexpressing/amplified (HER2+) metastatic colorectal cancer (mCRC): Primary results from the multicenter, randomized, phase 2 DESTINY-CRC02 study. J Clin Oncol (ASCO Annual Meeting Abstracts), 41(suppl_16). DOI:10.1200/JCO.2023.41.16_suppl.3501

Strickler JH, Cercek A, Siena S, et al (2023). Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. Lancet Oncol, 24(5):496-508. DOI:10.1016/S1470-2045(23)00150-X

Transcript edited for clarity. Any views expressed above are the speakers’ own and do not necessarily reflect those of Oncology Data Advisor. 

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