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Is It Feasible and Clearly Beneficial to Combine Immunotherapy Approaches?

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Drs. Leora Horn, Ben Solomon, & Jack West review the potential rationale and possible limitations of combining different immuntherapy strategies with one another.

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Dr. West:  I would say, one of the other really hot concepts at World Lung and various other meetings, is combinations with immunotherapy. And that can be two different immunotherapy agents, perhaps a drug like Yervoy (ipilimumab), which is a CTLA-4 inhibitor, that really targets a different part of the immune system, in combination with these immune checkpoint inhibitors, like PD-L1, PD-1 — or, as we have alluded a bit to, chemotherapy in combination with immunotherapy or targeted therapy. How excited are you by some of the combinations, starting with, say, the different immune therapies combined together — is this incrementally far better than any one of these drugs, and is it financially possible to do this in the world we live in?

Dr. Solomon: So, I think in melanoma, the combination data looks super exciting. I think the combination of ipilimumab and nivolumab looks really impressive, particularly in PD-L1 negative patients, and it has to be a said, even that data are relatively early data. We know that it improves progression-free survival, where we’re yet to find out whether this changes overall survival. In lung cancer, I think Leora probably has been involved in some of the studies, but I’m not sure that we’re at that stage with the data — we’re relatively early, and the early studies were hampered by a lot of toxicity in the patients, and I think at this meeting we saw some slightly different schedules that might have improved the toxicity. Leora?

Dr. West:  Of course, we do need to be mindful that melanoma patients are often quite a bit younger and healthier than your average lung cancer patient. So, what is your thought on this matter?

Dr. Horn:  I agree that the data is very early — the MedImmune with tremelimumab combinations, and the nivolumab and ipilimumab combinations, but the toxicity, I do think, is going to be a big issue for lung cancer patients. They are older, they’re just not as hardy, and the toxicities are not inconsequential when they do happen.

Dr. West:  Yeah, I think that it’s appealing to think that, maybe, combinations will work in a broader range of patients, in whom a single agent may not be enough, and that, hopefully in a few years, we will be able to predict, reliably, which patients are best served by a single drug, versus a combination, if we can find combinations that are tolerable.

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