Tag Archive for: treatment resistance

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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See More from EPEP SCLC

Related Resources:

Enhancing Collaborative Decision-Making in Small Cell Lung Cancer Care
Enhancing Collaborative Decision-Making in Small Cell Lung Cancer Care
Empowering Patients with Small Cell Lung Cancer: A Team Approach to Tough Conversations
Empowering Patients with Small Cell Lung Cancer: A Team Approach to Tough Conversations

Helping Patients Navigate SCLC Treatment: Tools, Transparency, and Supportive Care

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. 


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Waldenström Macroglobulinemia (WM) Treatment: Why Timing Is Essential

Waldenström Macroglobulinemia (WM) Treatment: Why Timing Is Essential from Patient Empowerment Network on Vimeo.

Waldenström macroglobulinemia (WM) is a rare slow-moving disease, so immediate treatment isn’t always necessary. WM expert Dr. Shayna Sarosiek discusses the “watch and wait” period and what criteria may indicate a patient is ready for therapy.

Dr. Shayna Sarosiek is a hematologist and oncologist at the Dana-Farber Cancer Institute where she cares for Waldenström macroglobulinemia (WM) patients at the Bing Center for Waldenstrom’s. Dr. Sarsosiek is also Assistant Professor of Medicine at Harvard Medical School. Learn more about Dr. Sarosiek, here.

See More From The Pro-Active Waldenström Macroglobulinemia Patient Toolkit

Related Programs:

Expert Advice for Newly Diagnosed Waldenström Macroglobulinemia (WM) Patients

Expert Advice for Newly Diagnosed Waldenström Macroglobulinemia (WM) Patients

When Is It Time to Treat Waldenström Macroglobulinemia?

When Is It Time to Treat Waldenström Macroglobulinemia?

Understanding Waldenström Macroglobulinemia and How It Progresses

Understanding Waldenström Macroglobulinemia and How It Progresses 


Transcript:

Katherine:

I understand that many people diagnosed with Waldenstrom’s may not be treated right away. Why is that? 

Dr. Sarosiek:

Yeah, so a lot of patients – actually, the majority of patients don’t need treatment right away for Waldenstrom’s. And even some patients, about 20 percent to 30 percent of patients a decade later still don’t need therapy. Because, as I mentioned, it’s really such a slow-moving disease that often patients will have no symptoms or very few symptoms for many years. And if that’s the case, we really don’t like to introduce treatments earlier than we need to.  

One, because you might introduce a therapy that adds toxicity or side effects that are making the patient feel worse than they currently feel. Two, the other reason we don’t want to treat too often if we don’t need to, is because it’s possible the Waldenstrom’s might become resistant to therapies and then when we truly needed something later, the disease might become resistant to things we used earlier.  

The other reason is, we don’t have any data that shows us that treating early improves survival. We know that patients with Waldenstrom’s have an excellent survival. And that’s only when treating when we need to. So, we don’t have any data that tells us we need to treat early. And so, really, the focus of Waldenstrom’s therapies is just to make sure that our patients maintain a good quality of life with their disease under good control. And we can do that in a lot of cases by not offering therapy early and just doing it when we start to see signs that there is something that needs to be addressed.  

Katherine:

Many of us have heard this term “watch and wait.” What does that mean exactly? 

Dr. Sarosiek:

So, watch and wait generally just refers to a plan to continue to monitor the patient. Often every three months or every four months in clinic, where we might just examine the patient to check for lymph nodes or an enlarged spleen. We ask about symptoms that might perk our ears up or make us think about progression of the disease. And we also check bloodwork.  

That can tell us what’s happening with the Waldenstrom’s. So, really, the exam, talking with the patient, getting labs every few months is a good way for us to keep track of what’s happening with the disease. So, we’re watching closely, but we’re waiting and holding off on therapy until it’s needed. 

Katherine:

Yeah. How do you know when it’s time to begin treatment? 

Dr. Sarosiek:

Great question. So, we have criteria that were designed. That physicians internationally follow to tell us when patients need treatment. Of course, those are just guidelines, so it’s often based on the guidelines and also each individual patient. But, for example, one of the main reasons why patients might require therapy is if a patient has anemia.  

So, we measure that with the hemoglobin. If the hemoglobin’s less than 10, and the patient has symptoms of anemia, then in that case we might need to offer therapy. Another common reason for therapy being initiated might be hyperviscosities. So, if the blood is getting thick, as Waldenstrom’s progresses and the IgM level is high, then in that case blood flow can’t happen appropriately. And so, in that case, we might need treatment.

Another side effect that patients with Waldenstrom’s can have is neuropathy. And so, that’s numbness, tingling, burning, loss of sensation. Usually starting in the toes and working its way up the feet and legs. If that’s progressing rapidly, if it’s causing the patient to not be able to do their usual activities, that’s another reason for treatment. So, we have these clear guidelines that tell us the things that we should be watching out for and then, it helps us to know when it’s an appropriate time to start treatment for patients.