Dr. Alder:
Welcome to Integrating Immunotherapy Across the Small Cell Lung Cancer Spectrum, an ASCO Post round table. I'm Dr. Laura Alder. I'm an Assistant Professor and thoracic medical oncologist at Duke Cancer Institute. Joining today are two of my esteemed colleagues, and I'll let them go ahead and introduce themselves.
Dr. Choudhury:
I'm Noura Choudhury. I'm a thoracic medical oncologist and Assistant Professor at the University of Chicago.
Dr. Cooper:
I'm Alissa Cooper. I'm a thoracic medical oncologist at Dana-Farber Cancer Institute in Boston.
Dr. Alder:
Great. Thank you both so much for joining me today. So we just, in our first case, discussed limited-stage small cell lung cancer, and now we'll discuss the management of de novo extensive-stage small cell lung cancer. And so we'll get right into it. Mr. RB is a 58-year-old who presents with worsening dyspnea, a 15-pound weight loss over the past 2 months, and worsening fatigue. He is a former smoker, about 50 pack-year history. He had a CT chest, abdomen, and pelvis, and that identified a 6-cm right lung mass, bilateral mediastinal lymph nodes, multiple liver lesions, and adrenal metastases. He had brain imaging, and that found three 1-cm asymptomatic brain metastases. A biopsy was done from the liver, and that confirmed small cell lung cancer. He's married, has two teenage children, and is a high school teacher with a good performance status of one based on the ECOG approach.
So Dr. Cooper and Dr. Choudhury, I think we've both seen these patients a lot. Tell me, how do you initiate that conversation, when you're telling someone extensive-stage small cell lung cancer? What additional testing is needed? What would that initial conversation be like? Whoever wants to start.
Dr. Cooper:
Yeah, I think this is a tough conversation to have. It does sort of depend on whether the patient has been aware of their diagnosis and has Googled and seen a lot of really dispiriting things online about prognosis or expected lifespan. Typically, in my conversations with patients, especially at the first visit, I'm really not bringing in expected lifespan or numbers into any of my conversations. Not to obscure any information from patients, but more so in a way because we have medians, but we don't have a crystal ball for the patient sitting in front of us, and we really don't have a good way to predict what's going to happen to them. So I always try to be hopeful and optimistic at the first meeting, until we have reason not to. And then I do try to be honest with patients about when we have reason to worry and when things look a little bit tough in the road ahead.
But at this initial conversation with a person with very good performance status, with young kids, we do try to hope for the best. I talk about the chemoimmunotherapy approach in terms of, there are a few people for whom immunotherapy works really, really well. We don't know who those patients are ahead of time, and there's no reason not to think it could be them. So I do try to maintain a lot of hope and optimism while talking about a very serious illness with some candor as well.
Dr. Alder:
Absolutely. Dr. Choudhury, any additional testing or referrals? And then if you could start discussing what you would talk about for treatment for this patient.
Dr. Choudhury:
Yeah. So to complete the workup, this patient in this case has already had an excellent workup. I think it sounds like, if I recall what you said, he had a CT scan. So I typically still also try to get a PET if time allows. I don't withhold treatment to get a PET, but I do like to have a PET just to fully understand the extent of disease. But luckily for the patient we have in question, they already had a brain MRI, they had a CT scan, we know that it's extensive stage. And so at this point, I generally am ready to start treatment, and I do try to start quickly.
I will say our general practice patterns are that many people are diagnosed in an inpatient setting because they are so symptomatic. They really are coming to an emergency room because their symptoms have become unmanageable. And so it is not uncommon that we actually start treatment in the inpatient setting, and that's a really unique feature of small cell. That is not something we commonly do across other cancer types, but for small cell, the teaching is still strong that, in many cases, you should not let that person walk out of the hospital without their first cycle of treatment.
Dr. Cooper:
I'd just like to piggyback on what Dr. Choudhury was just saying and also just make one additional point. Oftentimes when small cell lung cancer presents, it's a very symptom-heavy burden of disease. And so patients are often dyspneic, in pain, developing even over a matter of weeks to a couple of months. And so for that reason, I do actually also always recommend palliative care referrals at the beginning, even when I meet patients on the first visit. I do frame it hopefully as supportive care, symptom-based management, but that it is also important in coping with a serious illness to have that extra layer of support. We do know that palliative care in lung cancer is extremely important, and it's, I think, even especially more so important in small cell lung cancer.
Dr. Alder:
Yeah. Thanks, Dr. Cooper, for making that really good point. I think we've all seen the studies that show that early referrals to palliative care for lung cancer not only helps the patient to live better, but also longer. So I love that you brought that up, and even from the first visit or the first couple visits to bring that point up, as well as other supportive services, for someone with children, thinking about getting child life involved and such. So really great to hear about that supportive care point.
So getting into the treatment planning, we have IMpower 133 and we also have the CASPIAN study. Did one of you want to quickly walk us through those two pivotal trials? And then of course, the other option is a clinical trial that's new and enrolling. That's always very important to think about at every single time point for these patients, but would love to hear about the standard option that we have right now.
Dr. Choudhury:
Sure. So both the CASPIAN and the IMpower 133 trials are now, they were presented initially in 2018 and 2019, very close to each other, and they essentially set the standard of care as chemoimmunotherapy compared to chemotherapy alone. And so incorporating either atezolizumab or durvalumab with platinum etoposide chemotherapy improved overall survival both from about 10 months to a median of about a year. And historically that was a major advance for small cell, the first in 3 decades, and it really did set the stage for a very fortunate era in the last few years, where now we've had multiple advances. So in some ways we might be taking for granted that this is our standard of care, but it is actually only just a few years old, which is important to remember.
Dr. Alder:
Dr. Cooper, this patient does have some small brain metastases. They're not having any neurological symptoms or concerns, thankfully, but how do you approach this when you see brain metastases in front line small cell lung cancer?
Dr. Cooper:
Yeah, it's such a common clinical scenario. So unfortunately we do confront this quite a bit. Usually in the setting of small asymptomatic brain metastases, I usually just have a discussion with my radiation oncology colleagues, have them review the scan, make sure there's nothing worrisome about the location of the metastases or any sort of perilesional edema that is worrisome to them, and have them weigh in on whether they think it's reasonable to proceed with systemic therapy alone and then get a short interval follow-up scan. That's usually their recommendation, since we know that small cell lung cancer is so treatment sensitive, even in the brain at first. So chemo and immunotherapy can work really well for those small lesions.
We do have to be quite vigilant, though, because we know that they might recur or progress. And so actually we're not even usually waiting the full 6 weeks. Sometimes we might do a 4-week scan or something to be a little bit more conservative, but certainly regular close follow-up with MRI, and to make sure the patient knows any red flag symptoms if they should develop, worsening headache or any focal neuro signs, et cetera.
Dr. Alder:
Great point. If you did defer radiation at first, when would be your first follow-up scan?
Dr. Cooper:
Yeah, so certainly at least at that 6-week mark when you do your first full restaging, but if there's anything that's maybe a little bit more worrisome, maybe even 4 weeks just to make 100% sure. I think we're always trying to think about the long game for our patients, and how are we going to maximize and optimize their therapy all along? And so I think sometimes we think if we can push something down the road until it's absolutely necessary, that might be the best thing for the patient. Because if we've already irradiated brain metastases, then we might be burning a bridge for later down the road if they need more radiation or something else is happening to them clinically at that point in time. So we're always trying to think a couple of steps ahead of the cancer. We're not always successful, but we're trying our best in that strategy planning.
Dr. Alder:
Great, thank you. And then now of course we have another option, and that's the IMforte regimen that was presented last year at ASCO. And this adds lurbinectedin to atezolizumab after the patient's completed four cycles of induction chemotherapy, had restaging scans, did not show any signs of disease progression either in the brain or the body. And we know that this trial found significant improvement not only in progression-free survival, but also in overall survival. And this is an option now that we have, and it's an option that I try and discuss with the right patient pretty early on so they have a good roadmap of what could possibly be incorporated. Dr. Choudhury, I would love to hear how you discuss and your thoughts and who is the optimal IMforte candidate that you're seeing every day in clinical practice.
Dr. Choudhury:
Yeah, thanks so much, Laura. So definitely that first meeting, I also try to provide a roadmap of what to expect for the next few months, and I frame the IMforte regimen as a possibility. I try not to put too much weight on, this is definitely what we're going to do, because unfortunately the reality is that many of our patients lose significant fitness in the first few months of chemoimmunotherapy. Some patients might have disease progression or have other reasons that they're not eligible. And so I don't want it to be perceived as a failure if patients ultimately can't go on to get lurbinectedin plus ICI maintenance. I present it as an option, and I also present as an option that if we don't feel ready to start lurbinectedin at the start of maintenance, that there's always immunotherapy, monotherapy maintenance as another option.
My ideal patient to be able to get the IMforte regimen is somebody who gets through chemo-IO well, meaning that they don't have a decline in their performance status, they have response or at least stable disease on their restaging scans after four cycles of chemoimmunotherapy, and who aren't struggling with specific chemotherapy related adverse events that might limit their ability to start lurbinectedin. Specifically, the ones we worry about are cytopenias that are failing to improve in time to start lurbinectedin. But that's kind of my ideal patient. The IMforte trial actually excluded patients with any brain metastases. In clinical practice, I would not actually use that as a discriminator to say this person should not get the IMforte regimen. I think they just were excluded, but I don't think there's a plausible reason that a patient could not get the lurbinectedin plus ICI maintenance just because they had brain metastases.
Dr. Alder:
Agreed. That's a great point. So going back to our case, this patient received four cycles of the IMpower regimen with carboplatin, etoposide, atezolizumab, a good partial response, thankfully. Of note, though, there is some residual lung mass and mediastinal nodes on the follow-up scan. Dr. Cooper, why don't we start with you? We'd love to hear how you approach consolidative thoracic radiation in this setting.
Dr. Cooper:
I'm kind of smiling, because I want to know how I approach it as well. No, I think it's a challenging area, because this used to be 100% standard of care for patients who had a good partial response, who had residual thoracic disease, who had good fitness, this improved survival, to give thoracic radiation. And so that was 100% the standard of care prior to immunotherapy being the standard of care. That was the era in which those trials were conducted. And in general, I think I'm not entirely sure how we mix in thoracic radiation in the era of immunotherapy maintenance. I think for select patients, and if your radiation oncologist agrees that they're a good fit for it, I think still very reasonable strategy. I happen to not have many patients who just have thoracic disease, so I don't frequently employ it, but I do think it's not totally off the table.
The RAPTOR trial is actually exploring this question in a prospective manner, so it will be really great to get those data to really understand where radiation can fit in the immunotherapy era.
Dr. Alder:
It's a great point, Dr. Cooper, eager to see the RAPTOR trial. And speaking of recent trials, at ASCO this year, there was actually a clinical trial presented by Dr. Bjørn Grønberg looking at concurrent thoracic radiotherapy, chemotherapy, and durvalumab in extensive-stage small cell lung cancer. Dr. Choudhury, I would love for you to summarize this trial and your thoughts about how this is applicable to our patients today.
Dr. Choudhury:
Yeah, so this was a well-designed phase III trial where patients were randomized to immunotherapy plus chemotherapy, which is our standard of care, or chemoimmunotherapy plus concurrent thoracic radiotherapy. And interestingly, we had briefly discussed in the previous segment about how, in the limited-stage setting, concurrent radiation plus ICI might actually diminish the survival impact of ICI. We see potentially a similar trend here, where the patients who were treated with thoracic radiotherapy and chemoimmunotherapy actually had a decreased overall survival, and they also had worse toxicity. And so this trial, again, this is not typically what we do in practice, as Dr. Cooper was describing, which might be consolidative thoracic radiotherapy, but this trial provides good data that the concurrent strategy is not optimal to use in the setting.
Dr. Alder:
Yeah, that's a great summary. Thank you. Lots of moving points, lots of things to take into consideration whenever we're seeing patients. And so jumping back again to this patient, he was continued on atezolizumab maintenance therapy. Want to highlight the importance, as we've discussed a few times, of doing surveillance brain MRIs at least every 3 months for the first year or two.
And then go into a few of the key clinical takeaways. We went over the front line treatment strategies. We went over IMforte. We went over some of the nuanced information and decision making and consolidative thoracic radiation, and really want to emphasize the importance of supportive care and making sure that we support our patients every step of the way with palliative care, with organizations like Small Cell SMASHERS and things like that.
So this brings us to the end of this case. Please see the author segments for further discussion about the latest research in small cell lung cancer or visit ascopost.com. And thank you again to my two companions, Dr. Cooper and Dr. Choudhury, for having such an excellent conversation with me.
