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Emergence of Immunotherapy for Small Cell Lung Cancer



Philippa Cheetham, M.D.: Dr. Kim, you’ve been talking to us about the treatment options for patients with small cell lung cancer. We’ve talked already about radiation therapy. We’ve talked about the chemotherapy options, some of which have been around for many years and have good outcomes but not always as good as we would like. And now we’re on this horizon of immunotherapy for lung cancer. Can you tell us a little bit about what that means? What does immunotherapy mean versus chemotherapy, and how does that apply to treating small cell lung cancer?

Edward Kim, M.D., FACP: The concept of immunotherapy is really a fascinating one. I have to credit other people out there like Jim Allison [Ph.D.] and others, scientists who have made a huge impact in this area. We’ve always known the immune system is one of the most powerful systems in our body. It’s why when we step on a splinter, we don’t die from an infection.

Philippa Cheetham, M.D.: Hopefully not.

Edward Kim, M.D., FACP: Yes, it can happen but at least our immune system keeps us safe. Cancers are smart. I call them little terrorists because they can look like other cells, but they behave badly. And we can’t necessarily mind read in these cells. And they work against you. They want to harm you. And they’ve developed these defense mechanisms over time to evade the immune system. Your immune system’s surveilling the body, trying to see if there are bad cells and get rid of them. And these defense mechanisms or cloaking devices are helping the cancer cells evade them.

So what we’ve seen now is that these drugs uncloak the cancer cells. They get rid of that defense system. And, if you’re a “Star Wars” fan, it’s like turning off the shield of the death star or what have you because it’s not about using a chemical therapy to directly kill a cell. It is now trying to make it vulnerable so that other things like your immune system, like other chemicals can come in and destroy them. And so that is what’s fascinating about the field. It’s fascinating about science. Adding that to chemotherapy has proven to be beneficial, and we’ve seen that now with clinical trials that have reported data finally after decades of work, and believe me, there have been so many negative clinical trials out there. But I like the effort. We want to keep trying, and finally we’ve made some advances.

Philippa Cheetham, M.D.: As a patient, when I hear the words immunotherapy, I would think first of all, it sounds like a great idea because you’re using my immune system to fight my cancer. So it sounds much more targeted. It sounds much more focused. But it also, maybe I’m wrong, it sounds less toxic than chemotherapy that just blasts through everything with all the side effects that we’re so familiar with. Is that true, that immunotherapy is more precision-based and less toxic?

Edward Kim, M.D., FACP: I think the biggest toxicity we see is in folks who have a hyperactive immune system. What does that mean? We call those having these autoimmune disorders, bad rheumatoid arthritis, or lupus, or some of those conditions. That means that your immune system is a little hyperactive and a little out of balance. And those are the folks right now who we are being very cautious in giving these new checkpoint inhibitors to because they could have some very bad side effects. That’s who would have a predisposition. There are other folks, we don’t know what their immune system is like until we treat them. They can get diarrhea, they can get inflammation because of a hyperactive immune system. And people say, well, it’s good to have a strong immune system. Well, it’s good as long as it’s not too strong, right.

Philippa Cheetham, M.D.: To a degree, right. And we’ve learned so much about lung cancer from other cancers, and vice versa. These immunotherapy treatments you’re talking about, it’s not just lung cancer that we’re using them in. Other cancers where we’re seeing the use of immunotherapies, any comments on that?

Edward Kim, M.D., FACP: Everywhere. I mean it really started with melanoma, but now we’ve seen them in GYN [gynecologic] tumors. There was just an announcement recently in triple-negative breast cancer that we have an immunotherapy. Multiple in the GU [genitourinary] cancers, maybe more than we need, but there’s plenty of them at least. The example I give to people, if they haven’t seen the commercials on TV or anything, is Jimmy Carter. He’s got melanoma and he’s like 150 years old, and he’s been taking….

Philippa Cheetham, M.D.: Hope he’s not watching this.

Edward Kim, M.D., FACP: Well, all the love to Jimmy. He’s a great human being, and he’s really been a symbol for someone who was diagnosed with an advanced cancer in his liver and his brain.

Philippa Cheetham, M.D.: With a bad prognosis anyway, melanoma.

Edward Kim, M.D., FACP: That’s right, and now has taken therapy. Gosh, it’s probably his third year by now, just cooking right along. So there can be some good outcomes.

Philippa Cheetham, M.D.: But it was literally only a very few years ago that these drugs were first of all, not on the horizon and then very quickly they seemed to come out of clinical trials into clinical use. And many of them are already FDA approved.

Edward Kim, M.D., FACP: Yes. We always say that you shouldn’t have to do a long complicated study with large numbers of patients to prove a drug has a little bit of benefit. The drugs that really benefit folks, we’ll get them quickly because they’ll show signals that are very dramatic very quickly.

Philippa Cheetham, M.D.: For patients who may not be necessarily treated in specific centers, how easy is it for patients to get on these drugs where there’s been shown to be real benefit in terms of survival?

Edward Kim, M.D., FACP: It always can be when it’s preapproval. And right now we don’t have official first-line approval for atezolizumab, although by the time this is broadcast it might be. You never know how those timelines go in oncology these days. But there is so much data out there that maybe you’ll have to talk to your insurance company or payer. But this is the standard of care right now in patients who have extensive stage small cell, is a combination of carboplatin, etoposide and atezolizumab. And that is what we should be thinking of every patient who comes in unless they have some of those contraindications that we talked about with autoimmune histories or other things.

Philippa Cheetham, M.D.: It’s amazing, isn’t it, how these immunotherapies that were initially reserved for patients with very end-stage disease in all cancers, seem to be coming further and further toward initial diagnosis and early treatment.

Edward Kim, M.D., FACP: Yes. I think the studies now are focusing, just as you say, on early stage. We don’t know how much immunotherapy one needs. The early studies had people taking them for a year, but then there were so many people who were still doing well after a year, they had them continue to two years and now you stop after two years. But I’ve seen people who have had just a couple doses of immunotherapy and it’s had an effect because it, again, changes how your cancer presents, and it gives your immune system a new memory. And as long as those things stay constant, it’s not like taking a suppressive chemotherapy or a toxic chemotherapy to keep a tumor down. It’s your immune system doing the work.

Philippa Cheetham, M.D.: You’ve talked about combination use with other standard chemotherapies. Do you think we’re on the verge of dropping the standard chemotherapies and just giving patients immunotherapy, or we’re not there yet?

Edward Kim, M.D., FACP: People have asked me that question quite a bit. I love the fact that we’re using less and less cytotoxic chemotherapy in our treatments. We’re using targeted therapies, we’re measuring genes and markers in tumor types. But I think there will still always be a role for chemotherapy, just because it is a treatment and it has helped people. And so there will always be a role. I just want it to play more of the supporting cast rather than the primary.

Transcript Edited for Clarity

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