Should Immune Checkpoint Inhibitors and Other Therapies Be Combined Concurrently or Sequentially?

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Drs. Leora Horn, Ben Solomon, & Jack West consider the merits of administering immune checkpoint inhibitors concurrently with standard first line chemotherapy or targeted therapy vs. sequential treatment.


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Dr. West:  With regard to combinations of immunotherapy with conventional treatments, such as chemotherapy for patients without a driver mutation, or patients with a driver mutation who would otherwise get a targeted therapy, how optimistic are you about concurrent treatment, versus sequential? Do you think there’s a good reason to favor a concurrent approach, versus thinking that you would do just as well or better by just sequencing these independently, Leora?

Dr. Horn:  So, I’m not a big fan of the concurrent with chemotherapy trials. You know, there has been data presented a couple times showing that patients maybe have a greater response, but I actually question whether some patients even needed to get chemotherapy to begin with, and a lot of the trials, I worry, are comparing chemotherapy with or without immunotherapy, but there’s no arm that’s immunotherapy alone and, so, are you just getting the responses that you would have seen with immunotherapy if you had just used that up front? And there are a little bit more toxicities, when you’re looking at these combination trials.

Dr. West:  What are your thoughts, Ben?

Dr. Solomon:  Yeah, look, I think it’s still early, I think we had some encouraging data, although, just with respect to response rate, about the combinations of platinum doublets with PD-L1 inhibitors. I think Ross Camidge presented a study where, in a very small number of patients, the response rate with the combination seemed to be about 60%, which we would think would be higher than expected with chemotherapy, and I thought that was encouraging. Whether the sequence made any difference, I think, remains to be seen, and in that particular study, toxicities didn’t seem to be a big issue, but I think they’re early days, and I think patients may well respond to immunotherapy alone — and I think a question will be sorting out which patients can be treated with immunotherapy alone, and which patients won’t respond and do need combinations, either with other immunotherapy agents, or with chemotherapy.

Dr. West:  Right, one of the concepts is that perhaps the cell kill from chemotherapy, or a targeted therapy can lead to greater immunosensitivity — kind of prime the system, and lead to more robust immune responses, it’s something that hasn’t been tested really. I would say that, as we had started to discuss, it’s a pretty broad approach to clinical trials with immunotherapy, which is basically alone or in combination with everything, and every setting, of every cancer, and if there’s any upside of that, it’s that these will all be tested in the light of day, we’ll see what the data show. Right now, we’re pretty devoid of data and just speculating, but in a couple of years we’ll actually have data to compare and make some intelligent recommendations.


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