AACR 2026 | Watch-and-wait after HER2 therapy in rectal cancer: benefits and risks

Yeah, it’s a great question. So this is already being undertaken in many centers, even outside of the HER2 treatments. So, you know, the standard of care in many United States centers is to do induction chemotherapy and then radiation. And when those two modalities are applied, probably about somewhere between 20 and 40% of patients will actually have a complete response with both chemo and then later with radiation, those periods. And about like 20 to 40% will have a complete clinical response. And in our center and many centers, they’re watched without surgery. And most of those patients, probably over 80% of those patients continue to have a complete response and are de facto sort of cured. After five years, the cancer never comes back. But we decided to try and see if we can do that along with just medical therapy, so without doing radiation. So that’s why we had the off-ramp in our trial to, if a patient had a complete response to the chemo and HER2, they were allowed to not get radiation or surgery. So that’s why we did that in our trial. So I do think that this is possible. But one of the things we have to keep in mind is the local recurrence rate. As I mentioned, there were three patients that had a complete clinical response that had the cancer come back. One of the patients had it in a polyp, which was very small, and it was removed endoscopically, but the cancer did return. Another patient had radiation done. And the last patient that had a complete clinical response or recurrence is destined for radiation too. And so far, all those patients have not had their cancer return after those local therapies, but it does make you wonder how definitive this treatment is. Very important fact that we’re going to talk about is that all of the tumors that recurred were still HER2 positive, which is very interesting. So one of the conclusions that you could, one of the hypotheses we have is that maybe patients need longer durations of treatment. We treated patients for about five months, which is pretty long. It’s longer than we normally do for chemotherapy before surgery and rectal cancer. But in breast cancer, they treat patients for up to a year, both before and after surgery with HER2 treatments. So maybe these patients just need a longer duration of therapy. Their tumor had a marker, HER2 amplification, that indicates that they probably would still be responsive to HER2 treatments. So it’s definitely room for thought and sort of a broader picture of how well tyrosine kinase inhibitors do when integrated into the early stage setting for rectal cancer.

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