Second- and Later Line Treatment Options for Metastatic HER2+ Gastric Cancer
John Marshall, MD, reviews options for second- and later line therapies and considerations for treatment sequencing in patients with HER2+ gastric cancers.
John Marshall, MD: Beyond first line, there are a host of different treatment options that have come forward. We have taxanes. We have irinotecan. We have ramucirumab, a VEGF inhibitor. Until recently, we have not had a HER2 beyond-progression therapy that was showing any benefit. Front-line, yes. When we explored HER2, even combination HER2 therapy beyond first-line, we failed to demonstrate a clear clinical benefit. Therefore, your HER2 treatment was first-line and that was it. As you move from first- to second-line, there are choices. Now in a HER2-positive patient, we have newer data, fam-trastuzumab deruxtecan, which shows strong responses in benefit. That doesn't mean your taxanes aren't in play. It doesn't mean irinotecan is not in play or ramucirumab is not in play. This brings in another treatment option for our HER2-positive patients. Each of these regimens has the potential to cause a regression. You look at the patient in front of you and make decisions about where are they at the moment. What have their side effects been so far? How's their cardiac function?
If you can do repeat testing, is HER2 still overexpressed, or has some emergence of resistance come forward? Molecular testing will help you with that. It is not required in this setting but can be helpful. You take your known portfolio of treatment options and you look at the patient in front of you and make the best decision for that patient together. With gastric cancer, unlike colorectal cancer, we often don't get the chance to get many lines of therapy in. The disease, while it often is responsive to first-line therapy, it often is quite aggressive in subsequent lines of therapy. Very commonly get peritoneal carcinomatosis, which of course causes a significant decline in performance status, etc. We are developing new therapies, new HER2 therapies, new IO therapies, and we have new oral therapies with tipiracil/trifluridine. We are seeing people getting into second- and third-lines of therapies, depending on how serious the patient's cancer is at this moment, how life-threatening it is at this moment, and it gives you a sense of what card you should play in terms of sequencing. If you need a response, you have some choices. If stable disease is OK, you have some choices. I do think as we are doing in colorectal cancer increasingly in upper-GI [gastrointestinal] gastric cancers, we are thinking more of lines of therapy and sequential therapy and treatment sequencing.
This transcript has been edited for clarity.
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