Treatment Landscape for HER2+ Metastatic Colorectal Cancer


An overview of the treatment landscape for HER2+ metastatic colorectal cancer and recent updates to the NCCN Guidelines.


Cathy Eng, MD, FACP, FASCO: Dr Kamath, can you discuss the treatment landscape for HER2 [human epidermal growth factor receptor 2] metastatic colorectal cancer?

Suneel Kamath, MD: Yes. It’s a busy landscape for sure.

Cathy Eng, MD, FACP, FASCO: It’s a big question.

Suneel Kamath, MD: The first thing that came to mind as we discussed in the first case is the tucatinib [Tukysa]–trastuzumab [Herceptin] combination, which is the first to have FDA approval in the United States with the strongest data. It’s attractive as far as being a chemotherapy-free regimen, and it also has a great response rate of about 39%. Of course, there are a number of other molecules in the market. The next 1 that comes to mind is trastuzumab deruxtecan [Enhertu], or T-DXd, which has made a lot of waves in breast cancer and gastric cancer. That’s also a great option. That has a similar response rate, around 37%, and a similar disease control rate to the tucatinib-trastuzumab combination. But from a toxicity standpoint, that can be much harder in terms of myelosuppression, the GI [gastrointestinal] toxicity, and of course the ILD [interstitial lung disease] that we see with those agents as well. Patient selection for that is critical.

There have been studies for many other TKIs [tyrosine kinase inhibitors] as well: lapatinib [Tykerb] and trastuzumab [Herceptin], fedratinib [Inrebic] and trastuzumab. But when I look at those data, response rates are weaker and don’t seem to be as active. I don’t think there’s that much room for those in this space. Similarly, T-DM1 [trastuzumab emtansine] has been looked at as well. Those data aren’t that compelling either.

Cathy Eng, MD, FACP, FASCO: Thank you. This is an important time for us to mention the update and NCCN [National Comprehensive Cancer Network] Guidelines. Dr Parikh, previously pertuzumab [Perjeta] was listed as the first choice, but now we have this new FDA approval. How does somebody in practice incorporate these options?

Aparna Parikh, MD: With the approval and the data that we have with the MOUNTAINEER trial, Herceptin-tucatinib will be your second line plus the HER2-directed therapy option in the guidelines. We should confirm this, but it’s also listed for patients who aren’t chemotherapy candidates who are HER2 amplified as well. In the guidelines previously besides Herceptin-Perjeta, there was the Herceptin-lapatinib option as well. But given MOUNTAINEER, Herceptin-tucatinib has come out in front.

Cathy Eng, MD, FACP, FASCO: That’s a good point. I have an older patient with the borderline performance test who just tested positive. I’m going to proceed because she didn’t want chemotherapy. Although it’s approved in the refractory setting because she has a borderline performance status, we’re going to proceed with tucatinib first. Thank you for pointing that out.

Transcript edited for clarity.

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