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Targeting HER2 Outside of Breast Cancer

Insights From: William J. Gradishar, MD, Northwestern University; Sara A. Hurvitz, MD, UCLA Jonsson Comprehensive Cancer Center; Ian E. Krop, MD, PhD, Dana-Farber Cancer Institute
Published: Friday, Jan 31, 2020



Transcript: 

Sara A. Hurvitz, MD: The HER2 [human epidermal growth factor receptor 2] story really broke in breast cancer, but it is not the only cancer that has HER2 alterations associated with it. Gastric cancer, endometrial cancer, and other cancers have had HER2 alterations noted. In fact, in lung cancer, HER2 mutations are not totally uncommon. And so while the HER2 story is biggest in breast cancer, a number of other histologies have also had successes with HER2-targeted agents. There’s a basket trial looking at neratinib in all tumor histologies that have a HER2 mutation, and it’s showing very exciting results. I think we are moving from an era where our treatments were entirely histology based to a molecular-targeting or precision-medicine era where we choose a therapy and investigate therapies based on the molecular underpinnings of the cancer. As opposed to, where did the cancer originate?

William J. Gradishar, MD: Because there are so many more patients with HER2-positive disease in breast cancer compared with other subsets or other disease sites, it’s more likely that the clues that there may be activity of using these agents in rarer kinds of gastric cancers or ovarian cancers is really going to be derived from the breast cancer experience and then transported into those settings.

As you might expect, because there is a tiny fraction of patients with gastric cancer or ovarian cancer or lung cancer who express HER2, many of the drugs that we talked about today are being looked at and there are clinical trials. For instance, margetuximab is being evaluated. The antibody-drug conjugates are being evaluated in other diseases. And I think we’re likely to find that for things that work well in breast cancer, in those rarer subsets of other malignancies where HER2 expression is present, these drugs will be evaluated. Certainly, drugs that seem to work where there is a lower level of expression of HER2 are going to be particularly interesting to look at in these other diseases.

I think the experience in breast cancer will definitely inform how these drugs are potentially used in the rarer kinds of cancers that happen to have HER2 expression. And I won’t negate the possibility that if somebody found something in gastric cancer, we couldn’t apply it to breast cancer, but I think the flow of experience will go from breast cancer to other disease sites.

Transcript Edited for Clarity
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Transcript: 

Sara A. Hurvitz, MD: The HER2 [human epidermal growth factor receptor 2] story really broke in breast cancer, but it is not the only cancer that has HER2 alterations associated with it. Gastric cancer, endometrial cancer, and other cancers have had HER2 alterations noted. In fact, in lung cancer, HER2 mutations are not totally uncommon. And so while the HER2 story is biggest in breast cancer, a number of other histologies have also had successes with HER2-targeted agents. There’s a basket trial looking at neratinib in all tumor histologies that have a HER2 mutation, and it’s showing very exciting results. I think we are moving from an era where our treatments were entirely histology based to a molecular-targeting or precision-medicine era where we choose a therapy and investigate therapies based on the molecular underpinnings of the cancer. As opposed to, where did the cancer originate?

William J. Gradishar, MD: Because there are so many more patients with HER2-positive disease in breast cancer compared with other subsets or other disease sites, it’s more likely that the clues that there may be activity of using these agents in rarer kinds of gastric cancers or ovarian cancers is really going to be derived from the breast cancer experience and then transported into those settings.

As you might expect, because there is a tiny fraction of patients with gastric cancer or ovarian cancer or lung cancer who express HER2, many of the drugs that we talked about today are being looked at and there are clinical trials. For instance, margetuximab is being evaluated. The antibody-drug conjugates are being evaluated in other diseases. And I think we’re likely to find that for things that work well in breast cancer, in those rarer subsets of other malignancies where HER2 expression is present, these drugs will be evaluated. Certainly, drugs that seem to work where there is a lower level of expression of HER2 are going to be particularly interesting to look at in these other diseases.

I think the experience in breast cancer will definitely inform how these drugs are potentially used in the rarer kinds of cancers that happen to have HER2 expression. And I won’t negate the possibility that if somebody found something in gastric cancer, we couldn’t apply it to breast cancer, but I think the flow of experience will go from breast cancer to other disease sites.

Transcript Edited for Clarity
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