Understanding Immunotherapy Efficacy and Safety

Benjamin P. Levy, MD: We’ve won out with the development implementation of targeted therapies and immunotherapy, as well. We’ve changed the way we think about cancer treatment, and we’ve changed the way we think about tumor biology. The targeted-therapy paradigm is very straightforward. You identify a mutation, that mutation is either present or not, and you give the drug. You don’t give the drug unless you have the mutation. If you have an EGFR mutation, you have your choice of three tyrosine kinase inhibitors that are EGFR-directed therapies and that outperform chemotherapy. If you have an ALK-rearranged tumor, it’s the same thing. You’ve got three drugs now that you can use, and one is approved in the first-line. So, that’s a list of actionable mutations or genetic alterations that is growing in lung cancer, in which we now have targeted therapies.

It’s a bit of a clean story in the context of immunotherapy. Not to say that there are not competing strategies there, but I think the immunotherapy saga, as it’s just beginning, is much more complex. And trying to define those patients who are most likely to respond, trying to understand why patients don’t respond, is a much more challenging story. It has elicited a lot of healthy disagreement between medical oncologists about how to use these drugs. Nobody argues when an EGFR-positive patient walks through the door. They get a targeted therapy. But I think there’s a lot of argument about where these immunotherapies fit in. The data suggest second-line, but off-label use of nivolumab right now, from my understanding, is as high as 25% in the first line, which it does not even have an indication for. So, speaking again to the need of pathways, I think we’re just starting to understand immunotherapy. It’s a much more complex interplay between the immune system and cancer than it is with targeted therapies, going after a genetic alteration. And I think we’re still really learning.

I don’t think that the mode of administration impacts whether or not I will give immunotherapy. I think that’s something that I really haven’t considered. Yes, it’s great. When you have a patient who has a genetic alteration, you give them a pill and they don’t have to come back. But you still have to monitor them, though. They still have to come in every 4 to 6 weeks. These drugs aren’t magic bullets; they still have toxicity, so you’ve got to monitor those things.

With patients getting nivolumab, they have to come in every 2 weeks for an IV infusion. It’s 1 hour. And with pembrolizumab, they have to come in every 3 weeks for an IV infusion. But I think patients are so hungry for these drugs and they’ve heard so much about them, I don’t think any patient’s arguing, “Why can’t I get a pill versus immunotherapy?”, given how well tolerated these drugs are. Targeted therapies are very well tolerated, but immunotherapy is, as well. You have to keep in mind, most patients currently, who are getting immunotherapy, have been getting chemotherapy first.

These patients are getting chemotherapy every 3 weeks, their cancers are growing, and they’re not tolerating the chemotherapy. To give them immunotherapy, it’s a welcome change. And when it works, it’s a real welcome change. So, I’m not too concerned about patients’ reluctance or doctors’ reluctance to give immunotherapy based on its route of administration.