Dr. David Spigel:
Welcome to the ASCO Post Roundtable Series on the Emerging Treatment Options for Small Cell Lung Cancer. I'm Dr. David Spigel. I'm the Chief Scientific Officer at Sarah Cannon Research Institute in Nashville, Tennessee. I'm pleased to be joined by two close colleagues, Dr. John Heymach, the Chair of the Department of Thoracic and Head/Neck Medical Oncology at MD Anderson Cancer Center, and Dr. Lauren Byers, Professor in the Department of Thoracic and Head/Neck Medical Oncology at MD Anderson Cancer Center, as well. Lauren and John, thank you for joining us.
Dr. John Heymach:
Yeah. Morning, David.
Dr. Lauren Byers:
Thanks, David.
Dr. David Spigel:
Okay. Thank you. Here is case three. J.P. is a 69-year-old woman who presented to an outside hospital with increased swelling in her neck and face and hoarseness and dyspnea. She was transferred after a local CT identified a large mediastinal mass with scattered nodules in both lungs, I should mention. She was transferred to our center in Nashville.
We were able to get PET scan, which is increasingly harder in the inpatient setting. It revealed uptake in the mediastinal mass, and there were no distant lesions; specifically, these other lung nodules did not "light up". Pulmonary was consulted. EBUS was performed, and small cell lung cancer was diagnosed from the mass. A brain MRI was clear, and this patient was diagnosed with not only SVC syndrome but limited-stage small cell lung cancer.
Let's jump into this. John, I might start with you. For a patient like this that's symptomatic, in this case, SVC syndrome, what I find is the hospitalists/the other doctors involved in the care all tend to panic, usually. A lot of things tend to happen that I sometimes wish didn't happen. For me, I just think patients like this just need to start chemotherapy and don't need to run and do all these other things like a stent placement or even necessarily get radiation involved right away, although that's not a terrible option. Just your thoughts on someone who presents with SVC syndrome, remembering that hopefully they have curable cancer with limited-stage disease.
Dr. John Heymach:
Yeah. I think you're exactly right. I think there's a reflux when you've got something like an SVC syndrome to think about radiation right away. I think it's important if the diagnosis of small cell is to initiate chemotherapy quickly. The responses to small cell tend to be very quick, and, practically speaking, at least at our institution... I think it's going to be similar in other places. By the time you get a radiation team on board, you do simulation and all these other things, it's rare that you could really get radiation going all that quickly. Limited-stage small cell that's symptomatic like this... I agree with you. Get chemotherapy started, and then you can get the radiation consult team on. You can integrate radiation later with chemotherapy after a cycle of induction. In the vast majority of cases, you'll have symptomatic improvement within a week.
Dr. David Spigel:
Lauren, sometimes I take for granted the thought process of limited-stage vs extensive-stage, but it can be difficult sometimes. In this example, there's some pulmonary nodules that are outside the field of the mass. How do you think about the diagnosis? I was taught a long time ago, it's whatever the radiation oncologist can get in a field that makes it limited-stage. How do you approach it?
Dr. Lauren Byers:
I think that's my approach also. Basically, with limited-stage, it's, can it be covered in the field? I think that, logistically, especially in this patient who's having a lot of symptoms from SVC syndrome, I agree with both of you in terms of getting the systemic treatment on board as quickly as possible is going to provide symptomatic improvement, make it easier for them to be able to lie down for simulation, et cetera, and getting set up for radiation. The other thing I would say is it's not uncommon for us to see in limited-stage small cell lung cancers other findings on the scans, maybe something that might be pneumonia or these small nodules. I try to give patients the benefit of the doubt that unless it's very compelling that it is more advanced cancer that we're seeing on the scan, we want to really push forward in terms of a curative intent approach.
Dr. David Spigel:
John, this patient, actually, surprisingly, just some steroids, was able to go home before I even had to give chemotherapy. She came into the office. Within 7 days, we got it started. She is doing well. I was a little surprised. Our radiation oncologist... There's several we work with. He said, "David, I've talked to her and we're going to do twice daily radiation." Is that standard at your center? Certainly, the data show it is better than single daily radiation. It's just hard to pull off. Do you do that ever?
Dr. John Heymach:
Yeah. Just to review people, the role of hyperfractionated twice daily radiation vs once daily... It's a bit controversial. There had been earlier data, Turrisi study, that suggested that twice daily was more effective. More recently, there's been some studies that say really it looks like the two are pretty similar. There was just an NRG study... Jeffrey Bogart was the first author of this, that showed no real difference between them and actually a little more favorable toxicity with the once-daily, a little less esophagitis, and so forth. I think we have equipoise. We discuss both options with patients. Twice a day means you're essentially hanging around all day getting radiation. If patients are local and they'd like to get the radiation done more quickly, they'll do twice a day. But we're comfortable giving either one, and I don't think the efficacy differences are significant between them.
Dr. David Spigel:
Lauren, I'm sorry to bring up this old topic, but it's still a relevant topic because people ask about it. Let's fast-forward a little bit. I'm not quite there with this patient because she's only two cycles in. But as we get through, say, the last cycle of chemotherapy, do you give PCI or prophylactic cranial irradiation, and maybe why or why not?
Dr. Lauren Byers:
Yeah. That's a great question. I discuss it with all of my patients. But I would say more and more we're taking an approach of using close monitoring and observation with MRIs as opposed to PCI just because of some of the toxicities that can be involved in patient preference and the fact that now we can do, I think, high-quality monitoring with the MRIs.
Dr. David Spigel:
John, the patient, let's say, has finished chemoradiotherapy, has had a great response, is doing well from a side effect standpoint... Let's just say PCI was not given. Ahead of you now is durvalumab. A study called the ADRIATIC study showed it had led to an improvement in PFS and OS, but what I'm going to challenge you on is why not just give this patient tarlatamab?
Dr. John Heymach:
Yeah. Well, the first and obvious answer is we don't have data yet in the limited-stage setting. This is really where immunotherapy, I think, to some extent, shines in this setting for small cell. This is really where it's made the biggest impact, and to be really well-tolerated. It looks like giving immunotherapy... In this case, it's durvalumab from the ADRIATIC study, after completing chemoradiation. The benefit is really substantial. The tolerability is very good, similar to giving durvalumab in the PACIFIC setting for non-small cell after chemoradiotherapy.
It's interesting that giving immunotherapy concurrently with radiation has gone pretty poorly when you're radiating the mediastinum. We had the NRG study, the LU005, where there was no benefit seen, and the PACIFIC, too, where there wasn't seen. But in this setting, after you've done chemo radiation and you don't have a progressive disease, durvalumab gives a lot of benefit with very little problems in terms of tolerability. For me, the strength of the data for ADRIATIC is the reason to just follow that, as happened in that protocol.
Dr. David Spigel:
Lauren, is there a patient you would not give durvalumab to? Say, they've met all the criteria for ADRIATIC. They're looking well, so to speak. Is there somebody you wouldn't do durvalumab in, and who would that be?
Dr. Lauren Byers:
It would be very rare for there to be a patient who I did not think would be eligible to receive durvalumab. As John mentioned, the magnitude of benefit of adding durvalumab in the ADRIATIC study was incredibly significant and immediately changed the standard of care. We obviously ask patients about any history of other medical conditions: histories, complications, or things. But I think what we have found more and more over the last several years in lung cancer in general is that many patients, even if they have a history of an autoimmune condition, can safely receive and be monitored in terms of receiving immunotherapy.
Dr. David Spigel:
John, where do you think the next step forward is going to be in limited-stage disease? Where's there an opportunity?
Dr. John Heymach:
Yeah. I think now that the efficacy of immunotherapy has been established, I think in the limited-stage setting, I think we'll build upon it because it's clearly a huge improvement, but our cures are still relatively rare, or it's still a minority of patients who appear to be cured. I think looking at T-cell engagers like tarlatamab in this setting, can we really try to eradicate that little bit of disease that's left in the setting? I think that certainly makes sense.
We saw that lurbinectedin in the maintenance setting for extensive-stage is offering a huge benefit. Could it possibly offer a benefit in the limited-stage setting? I think that's a question that makes sense. Then, I think that it's a little bit early to look at things like antibody drug conjugates. Certainly, in the second-line setting, we're seeing really exciting results with the number of antibody drug conjugates, but they're not yet established in the extensive-stage setting. It's not quite time, I think, to look in the limited-stage setting yet there, but one could imagine in the future those will play a role as well. But we certainly have a deeper bench now for small cell than we've ever had in the past.
Dr. David Spigel:
Yeah, I agree. I think it'll be exciting to see what happens in the next few years, both in relapsed, extensive-stage, and limited-stage disease. Well, that wraps up this case. This patient is in the middle of their chemo/radiotherapy right now. Hopefully, we'll have a good path ahead. But a few key clinical takeaways. The first is that PCI or prophylactic cranial radiation is an option to help eradicate a cold disease in patients with favorable prognoses, and something that obviously should be discussed with the patient and their family in terms of pros and cons. Durvalumab is a relatively new standard of care following disease control with chemoradiotherapy in the limited-stage setting. Finally, tarlatamab is approved for relapse small cell lung cancer, but its role in the management of limited-stage or extensive-stage disease is unknown presently, but trials are in progress. 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.
