HER2+ Colorectal Cancer: Slicing the CRC Pie into Curable Portions

John L. Marshall, MD


May 23, 2016

Editorial Collaboration

Medscape &

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This is John Marshall from Medscape, on my new fancy recorder. I hope you're seeing my beautiful face much clearer and you can see how much older I am.

There is a really cool study that just came out on HER2-positive colon cancer.[1] We tried to do this 20 years ago, when trastuzumab first came out, and we said that there weren't enough HER2-positive patients out there. But now we're rethinking this. Given all of the broad molecular profiling that is going on out there, we're seeing more and more patients who are HER2 positive.

This investigative group had to screen 900 patients to find about 50 who were HER2 positive. That's only about a 5% hit rate. Those 5% went on this clinical trial and were treated with trastuzumab and lapatinib in a phase 2 study. They had a 30% response rate. One patient had a complete response. There were a bunch of patients who had a partial response and more who had stable disease. Basically, it was a clinically active regimen in the 5% of patients who were HER2 positive. They were also KRAS wild-type patients. This is what precision medicine is all about.

Over in the lung cancer world, they're claiming great success because they've begun to cut the pie of lung cancer up into smaller and smaller pieces. As a result, they have targeted therapy for a bunch of subtypes. That's what is going on over there.

The same is happening in gastrointestinal (GI) cancers, and colorectal cancer as well. The problem with GI cancers, so far, is that we don't have quite as many slices of the pie. We know that we have the KRAS wild-type group for EGFR therapy; that's 40% or so. We now have this 5% that is HER2 positive. We have another 5%-15%, depending on who you believe, that is MSI [microsatellite instability]-high, which might respond to the checkpoint inhibitors. The hope is that there will be more and more of these coming.

How are we going to go forward with this? Another source of tension in our world is that we are not being reimbursed when we send broad molecular profiling out. The payers are rightfully saying, "Why should we pay for that? Is that research or standard of care?" We're at this awkward interface where we want all of these broad tests, but we're not sure that we're going to get reimbursed, and the molecular companies that are supporting this are losing money as they're hoping that the world comes around to this type of broad profiling as the standard of care.

I want us to understand this tension and try to push for broader profiling. I think that is the right answer, fundamentally. The TAPUR clinical trial[2,3] from ASCO is right on point for this. If you've done broad profiling, the point of the TAPUR clinical trial is to get you access to these off-label drugs and to show that there is benefit, like they showed in this clinical trial. Really cool stuff.

We're making personalized medicine happen. Some issues are preventing us from making this successful at a more rapid pace, but we need to keep pushing. This is the way forward for cancer medicine: taking apart each individual patient's cancer and treating them with the right drug at the right time. That is precision medicine. That is the way we're going to cure cancer.

John Marshall for Medscape.


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