Turning the Tide: Clinical Insights Into a New Era of Small Cell Lung Cancer Treatment
Dr. Jacob Sands, Associate Chair of Thoracic Oncology at Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School, outlines breakthroughs in SCLC treatment, from the integration of immunotherapy in first-line to promising results in innovative clinical trials, including CAR T-cell therapy and antibody-drug conjugates.
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Transcript:
Dr. Nicole Rochester:
What are the most significant advances in the current treatment landscape for small cell lung cancer? Five years. And how are they impacting patient outcomes?
Dr. Jacobs Sands:
Well, thankfully, you know, there’s a lot to talk about in this space, especially if we’re including current clinical trials, because there are a lot of drugs in development that have shown really exciting results. But aside from that, I’m going to stretch a little more than five years, because it’s so meaningful. Is the immunotherapy drugs that are now part of our first-line treatment. These are drugs that, unfortunately, probably work well for maybe 20 percent of individuals. But amongst those in whom these work, they can work amazingly well. We have patients that are more than five years out from their initial diagnosis with widespread small cell lung cancer that have never gotten another treatment. They got chemotherapy and immunotherapy and that’s it.
They’ve not yet had another treatment. Their disease is controlled. Now this is an, unfortunately, smaller subset of patients that this is working like this for. But I mean, I’m stretching to say that we might actually be curing some people of their incurable disease with the incorporation of these immunotherapy drugs. So first-line setting chemo plus immunotherapy has been the standard of care. Now more recently we’ve seen the ADRIATIC trial. This was a trial in limited stage after chemo-radiation that now uses durvalumab (Imfinzi), one of those immunotherapy drugs after chemo-immuno it actually had a pretty impressive impact on survival on the time to the disease occurring as well as overall survival of patients made a really quite a big difference.
So that’s now the standard of care after chemo radiation for limited stage to then get immunotherapy for two years. But five years ago, also saw lurbinectedin (Zepzelca). This is another chemo agent, got a publication from that study that led to approval. This was 105 patient cohort within a basket trial. So single arm. That led to FDA approval of a new drug for small cell lung cancer. Lurbinectedin is a once every three week drug. It’s pretty well-tolerated. I think as far as chemotherapy drugs work, it does not have a lot of the toxicities that people worry about. There are some things to monitor, but generally it is a manageable side effect profile as a new drug. More recently, we have tarlatamab (Imdelltra). This has made big headlines and it was a trial that enrolled in the third line and beyond. But the data was so good it got approved in the second line. So, you know, I often quote that about half of patients that get the drug benefit from the drug. It’s 40 percent that have a response–response meaning that it shrank by more than 30 percent. And amongst those individuals, 43 percent of patients were still on the treatment at the time of the last data kit.
And that’s beyond a year of ongoing treatment and some quite a bit more. So we don’t yet know the ceiling as far as how long this drug can work for. When it’s working. I mentioned about half of patients benefiting, but the response rate being 40 percent. That’s because even with stable disease, meaning that it could have shrank by less than 30 percent or grown by less than 20 percent. But in that range we see disease control and some portion of that out beyond six months, which I think is meaningful in the third-line and beyond setting. Now, of course, what patients want and what we want for them is for something to work for years, not just for months now, you know. But if something works for six months even, and then you have something else that works and then something else that works and something else, then you can string that out to a much longer timeframe. But it’s exciting to see potentially years of benefit from another immunotherapy drug. Now, with that being said, there’s a lot going on in clinical trials that’s quite exciting too. And I’d say one of the benefits at Dana-Farber as well as some of the other bigger academic centers is that we have multiple trials for small cell lung cancer.
One right now is CAR T. So this is essentially collecting the immune cells from patients. We send those off and process them so that they are trained essentially to recognize small cell lung cancer cells. And then we infuse those back into patients. So patients get their own cells back, but now are essentially trained to find small cell lung cancer cells and kill them. So the treatment is essentially training someone’s own immune system to do the work. And it’s exciting. We’ve enrolled patients on that now and to see that technology now coming into the space on top of multiple drugs, which we call targeted chemotherapy. These are essentially chemo that is bound to an antibody, so that goes and finds a certain receptor on the surface of cells where it then pulls that compound into the cell. And so the chemotherapy is delivered into the cancer cells instead of just going everywhere. And that’s another whole class of technology that’s happening in clinical trials. Now, that’s a bit of scratching the surface as far as clinical trials. There are multiple other things that I could go into, but trials options, I think, are a really important consideration in the small cell space.
I’d say, at this point, especially if you combine what I just said about the past five years now with what’s going on in available clinical trials, there is more happening in the small cell space of novel, effective treatment options than the history of everything up to this point. And so it’s really exciting to see that as an option for patients and to see people do well for such extended periods of time.
Dr. Nicole Rochester:
Wow, that is extremely exciting. When you talked about curing an incurable disease, that’s when you really got my attention.
