Dr. David Spigel:
Welcome to The ASCO Post-Roundtable Series on Emerging Treatment Options for Small Cell Lung Cancer. I'm David Spigel. I'm a medical oncologist and am the Chief Scientific Officer at Sarah Cannon Research Institute in Nashville, Tennessee. Joining me today are two of my close colleagues. I'm excited to be having a discussion with them. First, I'd like to introduce Dr. John Heymach from MD Anderson. John.
Dr. John Heymach:
Hi, morning, David,
David Spigel:
And my second close colleague is Dr. Lauren Byers from MD Anderson. Thank you, Lauren.
Dr. Lauren Byers:
Thank you, David. Great to be here.
Dr. David Spigel:
Today we'll be discussing the treatment and management of small cell lung cancer with three patient case studies. Our first installment will focus on the treatment of relapsed small cell lung cancer. So let's dive into the first case.
So, K.G. is a 62-year-old woman who presented to an outside hospital with low back pain, thought to be related to a pretty bad motor vehicle accident in the fall of 2024. At that time, CT showed multiple lytic lesions and fractures, as well as a left lower lobe mass. Pulmonary was consulted, and EBUS was performed, which confirmed small cell lung cancer, and brain MRI was clear. She was in the hospital and was unable to get a PET scan, but she had evidence of widespread disease on the CT scans. It was a little confusing to know what was related to her motor vehicle accident and what was likely cancer.
Nonetheless, a diagnosis of extensive-stage small cell lung cancer was made, and she received four cycles of carboplatin, etoposide, and atezolizumab, and she achieved a clinical and radiographic response, a near complete response. All treatment—or chemotherapy, I should say, ended in February, 2025. She lived about 2 hours from me, and so at that time, she asked if she could transfer her care to a local medical oncologist, so I arranged that for that physician to just resume maintenance atezolizumab on a monthly schedule.
I hadn't heard from her for a while. I told the doctor to stay in touch if anything had come up, and it sounds like everything was going well until just recently. She showed up at our hospital—and actually at the moment, she still is in our hospital. She presented as a transfer with increasing back pain and dyspnea, and CT scans revealed a large left pleural effusion and now a mass again that had previously responded and shrunk, not disappeared, but had gotten remarkably smaller. We repeated a brain MRI here, and that was clear, and she had a thoracentesis for relief, and cytology confirmed small cell lung cancer.
When patients present, in my experience has been, it's often at a time of crisis, and usually it's in the emergency room and in a hospital setting. Is that true for you guys, John? Is that a common way for you to find small cell lung cancer?
Dr. John Heymach:
Yeah, David, I think among all the cancers we treat, small cell is the one that is by far the most common for people to end up in the inpatient setting for people that present with SVC syndrome with sudden collapse of lung, with really aggressive symptoms pretty often. And so sometimes we have that added complication of having to start treatment in the inpatient setting where you don't have... Commonly, there's problems that inpatient team may not be as accustomed to giving immunotherapy, for example. That's an issue sometimes. Sometimes it's harder to get molecular testing in the inpatient setting or things quickly, but when that happens, it's commonly small cell.
Dr. David Spigel:
Lauren, when you get to that point of finishing chemotherapy, whether it's four or six cycles, and you move to maintenance therapy, does anything change in the way you manage patients? Is it just once a month visits and periodic scans? Do you do anything different?
Dr. Lauren Byers:
I'm usually seeing them about every 3 weeks just to monitor initially for toxicity, and then as it gets a little bit further out and if it's looking like their symptoms are controlled and that they're having good quality of life, no significant toxicities, then we start to stretch that out and often are bringing them back about every 6 to 8 weeks to do imaging and monitor for response and any potential recurrences that might be going on.
Dr. David Spigel:
Just out of curiosity, when you're in that surveillance period—and I'm a little bit weird about this so I'll tell you I do this, but I respect a lot of my friends that don't do this—do you get MRs of the brain at the assessment periods, or do you just do chest CT scans, and then if they recur then you'll do the expanded surveillance?
Dr. Lauren Byers:
Yeah, we do get regular MRIs of the brain to monitor. Typically, it depends, of course, on if they're having any symptoms or other history, but I would say we're usually doing it at least every 3 months to monitor for any new brain metastases and try to identify those hopefully before they're developing symptoms.
Dr. David Spigel:
I find if I just say the patient's having a headache, I can usually get it covered. Hey, John, a lot of exciting data emerging in many tumor settings about surveillance with cell-free DNA. Is there a role for that in small cell lung cancer in this setting where somebody's achieved remission, and you're watching them closely?
Dr. John Heymach:
Yeah, ctDNA is really interesting in this setting because out of all the tumor types, small cell actually sheds the most. So in virtually everybody with extensive-stage disease, you can detect circulating tumor DNA. Now small cell doesn't usually have driver mutations, although we do look for mutations in the beginning because sometimes you find out that it's a transformed EGFR-mutant tumor. But even though you can always detect it, I don't tend to use it a lot in this setting for maintenance just because the likelihood of recurrence and relapse is so high. I'm usually just using radiographic markers, and I usually do the brain MRI every other, but you certainly could do it every one because we know the likelihood of brain menses is so high. But yeah, I just stick with radiographic markers. It's usually not a diagnostic mystery when it's coming back.
Dr. David Spigel:
Right.
Dr. John Heymach:
If something looks like it's coming back for small cell, it's usually... If it's quacking like a duck, it's usually a duck, unfortunately.
David Spigel:
And John, one more quick question about maintenance immunotherapy. Is your strategy to just you continue it indefinitely? Do you try to achieve a year or two years?
Dr. John Heymach:
Yeah, it's a great question, and this would've seemed like a question that was irrelevant a few years ago, where we'd give chemotherapy and then just wait for it to relapse, but I actually have a sizable cohort of patients that are just on maintenance immunotherapy that are now coming up are 2 or 3 years. It's a surprisingly large group, and we see that there's a big tail on the curve. I discuss it with the patients. I've got a couple of them that I'm treating right now that are past 2 years, and I say, "Listen, we don't have a lot of data after this point, but here's the pluses and minuses of continuing or not continuing," and all the cases so far, we've continued in every single one. I haven't had a single patient who is willing to discontinue it so far.
Dr. David Spigel:
Yeah, yeah, it's a pretty similar experience. So Lauren, here we are, and this is reality. This is a patient that actually is in the hospital right now as I mentioned, and so my choices are a little limited in the hospital, and remember, she lives very far away and has limited resources with travel. So I can get chemotherapy in the hospital, and so I chose to give her carboplatin/etoposide in the hospital to "get her started." I can't give her immunotherapy, I can't give her lurbinectedin or tarlatamab where I'm at in the hospital setting. Once she's out, I can do that. Just curious about if you're going to give platinum/etoposide again, number one, would you even give it, and how do you decide when to give it vs some of our newer options?
Dr. Lauren Byers:
If she's doing well in terms of her symptoms then... And again, it sounds like there's limitations in terms of logistics. I think this is something that we're seeing a lot more of when we're thinking about what to do in the second-line setting. We are using tarlatamab quite a bit, and we are seeing in our real-world population that it generally is well tolerated, but we also see that there are many patients where getting to a center where they can receive it and the travel and those types of things are very challenging. So I think in that setting, re-challenge would be an option, especially because she's out more than 3 months. In fact, it seems like close to...
Dr. David Spigel:
Yeah, it was about 4 months, I think.
Dr. Lauren Byers:
So I think that would be an option. And also since she's having symptoms, it may be something that could give some rapid improvement, although we would expect that the benefit from that is going to be pretty limited and brief. And so I'm sure you'd be setting up what your next line of therapy would be to try to go forward from there.
Dr. David Spigel:
So yeah, let me just carry you a little bit further there, so that is my plan to get her out. So what would you go to next? And then one more quick question about it. If your hospital had atezolizumab or durvalumab available, would you have added it back in here?
Dr. Lauren Byers:
Yeah, so I think this is where people have different approaches that I would, for somebody who is on anti–PDL-1 with atezolizumab or durvalumab, then I will add back in the chemotherapy if I'm going to re-challenge and continue the immunotherapy.
Dr. David Spigel:
And then the patient gets out of the hospital, and you've got everything ahead of you, which is more chemotherapy with immunotherapy, you have tarlatamab available, and you have lurbinectedin or anything else you want, what would be your choice? Would it be tarlatamab?
Dr. Lauren Byers:
Yeah, I would go to tarlatamab for this patient. I think that the data from ASCO and what's been published in terms of the second-line setting, I think is really compelling in terms of the clinical benefit. And I think what we're seeing is that in our real world population, as well as in some of the trial data, is that generally speaking, while it can have significant or toxicities that are sort of specific to cytokine-release syndrome or other immune-mediated toxicities, most patients are tolerating it well. And so I think that that tarlatamab, especially with the magnitude of benefit and the potential for a longer duration of response, is something that I would definitely try to go to for patients that can do that.
Dr. David Spigel:
John, as we finish up here, is tarlatamab your choice? And if you could talk a little bit about some of the challenges of giving that.
Dr. John Heymach:
Yeah, well it's great to have choices, and this is pretty different than even just a couple months ago, the way this is all emerging. For somebody in this situation like you're presenting here, we've got a few choices. So one is retreatment with platinum doublet here, and that's something that I view on a spectrum of how much benefit they've received, how well they tolerated it, the depth of their response. This sounds like somebody who did initially have a good response and then is now recurring the pleural effusion, and I'm more apt to re-treat now with platinum doublet because we're typically only giving four cycles of carboplatin/etoposide.
You remember, David, it used to be back in the day, we'd almost always go to six cycles.
Dr. David Spigel:
Yeah.
Dr. John Heymach:
We'd more often be using cisplatin. People were much more heavily pretreated. But after only giving four of carboplatin, usually people can tolerate another go around, so if people have had a longer duration, if they've tolerated it well, had a really good response, I'm more apt to go back to carboplatin and etoposide retreatment, as long as that interval has been at least three months. If it's been more than 6 months or 9 months, I'm very likely to go back, especially if they did pretty well with it.
Now competing with that, we've had recent good data with lurbinectedin in the maintenance setting and in the second-line setting, but really from ASCO, the data for tarlatamab in the recurrent setting and its OS benefit was really impressive. So I am much more apt to go to tarlatamab now sooner now that we have the survival benefits we've seen.
I think one of the challenges, it's not trivial to manage cytokine-release syndrome. It's not something that a lot of us solid tumor docs have a lot of experience with, so it does require admission in the inpatient setting for at least the first couple cycles, so our inpatient team has gotten a lot of experience and we've gotten a lot of experience with it, but it isn't trivial, so I think there's been a learning curve with tarlatamab. So clearly effective but some things that really do require learning how to manage CRS and some of the other side effects.
Dr. David Spigel:
Well great. I'll let you know that she got her first round of chemotherapy about 10 days ago, and she's thankfully feeling a little better and hopefully going home very soon. So that wraps up our first case. Here are some key clinical takeaways. The first is that platinum/etoposide can be used again when there was an initial benefit and when enough time has elapsed between cessation of that first therapy and relapse, at least 90 days. Also, the role of repeat immunotherapy is unclear when being used again with platinum etoposide but certainly a very standard approach in relapse disease as in this case. And finally, tarlatamab and lurbinectedin are also good options for relapsed small cell lung cancer when or if chemotherapy is not an option.
This brings us to the end of this case. Please see the other segments for further discussion about the latest research in lung cancer or visit ascopost.com.
