Immunotherapy in Small Cell Lung Cancer

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Kristie L. Kahl: To start, can you discuss how immunotherapy works in small cell lung cancer treatment?

Wade T. Iams, MD: Immunotherapy in the treatment of patients with small cell lung cancer is typically used in 2 settings currently, either right away and individuals who have stage 4 or extensive-stage small cell lung cancer in combination with chemotherapy. The idea being in those individuals who, in most cases, we're going to get the cancer to shrink with chemotherapy. We want the immune system to be stimulated to assist with cancer control in individuals with stage 4 disease, in individuals who we're attempting to cure with small cell lung cancer, with most commonly a combination of chemotherapy and radiation, or surgery, followed by chemotherapy, those individuals are eligible for immune therapy. If the cancer comes back, we would typically consider treating them with a combination of chemotherapy plus immunotherapy when the cancer comes back, again to attempt to amplify the immune system's role in cancer control at that point.

Kristie L. Kahl: What are the types of immunotherapy that we're using to treat small cell lung cancer?

Wade T. Iams, MD: Currently, the type of immunotherapy that's FDA approved for the treatment of patients with small cell lung cancer is targeting PD-1, PD-L1. The way to think about those molecules is that they provide a break on the immune system and the drugs we have take that break off of the immune system, thereby accelerating it to attempt to control the cancer.

Kristie L. Kahl: Are there any other types that are currently under evaluation for small cell lung cancer?

Wade T. Iams, MD: Yes, there is a broad field that is seeking to reprogram T cells, which are a component of the immune system. That's critical in identifying either viruses, bacteria or cancer cells, and then infuse those manufactured T cells against the cancer. That's one broad strategy. A second broad strategy that's being evaluated in small cell lung cancer and other cancer types is a concept of dual antibodies that seek to not necessarily reprogram the T cells, but rather use antibodies, which can act as magnets to pull T cells directly to cancer cells to see them. And so those are two examples of new immune strategies that are being evaluated in patients with small cell lung cancer, as well as a number of other cancer types.

Kristie L. Kahl: From the multidisciplinary approach, how can other therapies also play a role with immunotherapy; for example, like chemotherapy?

Wade T. Iams, MD: We think that chemotherapy in combination with immune therapy may help with the body's recognition of the cancer, because chemotherapy induces cancer cell death and fragments of those cancer cells are exposed in the immune system. So it may be more beneficial to combine the two. What we have to look out for is the reality that when we combine different cancer treatment types, almost across the board, it comes along with increased side effects. So we have to make sure that when we administer chemotherapy with immune therapy, that doesn't result in increased side effects. There are even clinical studies of combining immunotherapy with radiation in people with small cell lung cancer in early studies that has not looked like it adds significant side effects, but there's always a risk and we're always seeking to treat cancer better, particularly small cell lung cancer, which is so aggressive and difficult to treat. And we are combining what we have to be keen to monitor for is the increased side effects that come along with combining different types of treatments.

Kristie L. Kahl: What do we have to look forward to with immunotherapy moving forward in the small cell lung cancer space?

Wade T. Iams, MD: I think the big development on the horizon in patients with small cell lung cancer receiving immunotherapy is whether individuals, who are treated for cure typically with chemotherapy and radiation, derive benefit from further immune therapy after they complete the chemotherapy and radiation. We know that, in patients with non-small cell lung cancer who are treated for cure with chemotherapy and radiation, (the data on) the addition of immune therapy after that treatment is not completely mature or finalized yet. But it does look like that is going to increase cure rates in patients with non-small cell lung cancer. And there are multiple large clinical studies looking to apply immune therapy in patients with small cell lung cancer after they complete chemotherapy and radiation. In my opinion, that would be the biggest change within the field as far as the application of immune therapies, the early development of other immune therapy strategies is, I think, a little more uncertain at the moment.


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