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. Pleased to be joined by two close colleagues, Dr. John Heymach, the Chair of Department of Thoracic/Head and Neck Medical Oncology at the MD Anderson Cancer Center, and Dr. Lauren Byers, a professor in the Department of Thoracic/Head and Neck Medical Oncology at MD Anderson as well. John and Lauren, thank you for joining us this morning.
This is a case of a newly diagnosed patient with extensive-stage small cell lung cancer. Let's jump into it. TB is a 66-year-old gentleman who presents with neck swelling. A CT scan reveals a right upper lobe mass, mediastinal adenopathy and liver lesions. He admits to weight loss but no dyspnea, no hemoptysis and he has some right scapular pain. In the hospital where he was diagnosed a brain MRI was obtained and it was clear. Pulmonary was consulted, EBUS was performed, and small cell lung cancer was diagnosed. He remains in the hospital and a diagnosis of extensive-stage small cell lung cancer was made. We'll just jump right into it. Maybe Lauren, I'll start with you. What is your preferred upfront regimen? And remember this patient is in the hospital, if that influences your choices of agents.
Dr. Lauren Byers:
I think for this patient, similar to the first case, we want to get patients going in terms of their systemic treatment, especially with the chemotherapy, as quickly as possible. In this patient, my preference, depending on the patient's other medical conditions and lab work would be to start with cisplatin and etoposide.
Dr. David Spigel:
And when you're in the hospital setting, and MD Anderson is probably maybe a little different than say many community facilities, do you have access to immunotherapy in the hospital?
Dr. Lauren Byers:
We do. We're able to start patients both with chemotherapy as well as immunotherapy, depending on what their needs are. But I know that that's also quite different from many other inpatient services where often the chemotherapy will get started as soon as possible and then when they're discharged and being managed on an outpatient setting, then often immunotherapy will be added at that point.
Dr. David Spigel:
John, we have two available first-line immuno options, platinum/etoposide with durvalumab and the same with atezolizumab. Is it a coin flip for you or do you have preferences over which regimen you choose?
Dr. John Heymach:
Yeah, I have complete equipoise between these two regimens. The clinical data is very similar between them, so I use both of them, both the CASPIAN regimen and the IMpower133 regimen with atezolizumab and durvalumab. I think the clinical data is more similar than different between them.
Dr. David Spigel:
Several years ago now lurbinectedin came onto the scene a little bit, at least for me, under the radar. And then it was available as a relapse agent as a preferred option, at least for me, over a drug like topotecan. But recently we've seen data at ASCO, Dr. Luis Paz Ares presented data showing the value of a maintenance strategy with lurbinectedin. Patients receive platinum/etoposide and atezolizumab and then would go on to receive lurbinectedin and atezolizumab. The results were pretty impressive. I should mention this is not an FDA approved strategy. Do you expect this to become an approved strategy and is it something you would choose?
Dr. John Heymach:
Yeah, well, just to review the study you're discussing is the IMforte study and this is using chemotherapy with the atezolizumab and then patients who did not have progressive disease after induction chemotherapy with four cycles were randomized there to just continue standard maintenance with atezolizumab or atezolizumab with lurbinectedin. And I share your opinion, I think the results here were pretty impressive. It was a positive study and it was positive for both progression-free survival and overall survival. And for PFS, the hazard ratio was 0.54, it's a pretty big difference here. And overall survival here was 0.73. In other words, the benefit of adding lurbinectedin in the maintenance setting was as large in terms of overall survival as the benefits of adding immunotherapy in the first place to chemotherapy.
This is not yet an approved regimen, but based on that magnitude of benefit, if we assume that it will be approved to use lurbinectedin in the maintenance setting in the first line, it's something I absolutely would embrace and use given that magnitude of benefit. And I think the side effects here were what was expected. There were no new safety signals. Lurbinectedin does increase the number of adverse events, but they're predictable and overall fairly manageable. I'm pretty enthusiastic in seeing the results there in that first-line setting.
Dr. David Spigel:
Lauren, I was surprised by the results in some ways, in some ways not because we used to call these studies, the switch maintenance therapy. Remember a study where this was done with docetaxel as well. But nonetheless, I think this was pretty impressive results. Do you think if this was available to you today, a maintenance lurbinectedin option, there would be folks you wouldn't give that to?
Dr. Lauren Byers:
I think that that's an important thing to consider in terms of this drug is that while the survival benefit is clear in terms of adding the lurbinectedin in the maintenance setting, but does come with certain toxicities and symptoms that'll be needed to be gauged depending on both what the patient can tolerate and then also what the patient's preferences are. I think that that's something, there's typically chemotherapy-like side effects which are manageable for many patients, but that's something to consider. The other consideration is that treatment with lurbinectedin, depending on the site where they're receiving it often either requires or recommends either a central line or a port for administration. That's, again, just a logistical consideration. But I think those are some of the things that patients need to be aware of in terms of what potential side effects or logistics may be involved with the treatment.
Dr. David Spigel:
Lauren, I think this was a clever design where you wonder if lurbinectedin was substituted with some other drug, it still would've won at least for PFS. We have another agent out there that we're excited about, it's tarlatamab. It's been on the market now for well over a year. Its setting is in the relapse setting. I think everyone is pretty excited about tarlatamab's benefits and it feels in a way like lurbinectedin jumped over tarlatamab into a maintenance setting. Just to ask, do you think you could just say, well, I'm going to give tarlatamab and not lurbinectedin? Are there data coming to tell us it's going to be something we can use earlier than waiting for relapse? And for now, do we have to just wait until after lurbinectedin?
Dr. Lauren Byers:
There will be data coming in terms of using tarlatamab earlier in the front line setting. I think that'll be very useful to see what that looks like and that may really change the standard of care in terms of using it earlier. I agree that tarlatamab has definitely been very impressive in terms of the second line setting with the data that was presented at ASCO in the DeLLphi-304 trial. The hazard ratio was 0.6 and the median overall survival in the patients that were receiving tarlatamab was around 13 months vs around 8 months in the chemotherapy patients. I do think that that data really is striking in terms of the benefit in the second-line setting and so I think that's a good option as well. And I do think given the differences in terms of how the management is and currently requiring hospitalization for the initial treatment with tarlatamab, maybe a consideration logistically vs with lurbinectedin maintenance and thinking about the toxicities and other administration details related to that.
Dr. David Spigel:
John, you're not a gambler, I don't think, but if you were a gambler, would you bet that tarlatamab is going to be a first-line option and then what does that regimen look like in the first-line setting?
Dr. John Heymach:
The tarlatamab second-line results we've seen, the DeLLphi-304, as Lauren mentioned, are really interesting because the PFS differences are not particularly striking, they're less than a month, but the overall survival differences are really striking. You're adding more than 5 months of overall survival difference in that second-line setting. It seems to me likely that if you move this into the first-line setting, there will also be an overall survival benefit with tarlatamab. Now, there's a couple ways the regimen could be given. It's being tested both in the maintenance setting, similar to lurbinectedin in the IMforte study and also using it right from the beginning. I'm not sure which of those strategies is going to be best. I think giving it with chemotherapy, it makes you wonder if chemotherapy is going to mitigate the effectiveness of all these T cells that you're stimulating to attack the tumor. And the side effects of tarlatamab might be better after induction chemotherapy where you've reduced the tumor bulk, you might get less cytokine-release syndrome and so forth.
If I had to speculate, I'd speculate that we're more likely to use it in the maintenance setting after initial chemotherapy. Chemotherapy is effective in the vast majority of patients for shrinking small cell, reducing the tumor bulk, improving symptoms. We just know the duration of that response isn't great, and I think that's where tarlatamab really could add benefit. But we have lurbinectedin also providing benefit there as well. I think we have one exciting result already, and it won't surprise me if we have exciting results with tarlatamab in the first-line setting as well in the near future.
We look forward to what we're seeing. It's a big change after decades of no progress in first-line small cell. And David, you and I have been treating small cell for coming up on a quarter of a century here since our training. To think that it pretty much looked the same for the first 2 decades and now within a 1-year period we're getting all this rapid progress. It's rewarding.
Dr. David Spigel:
And very exciting. Couldn't agree more. I'll just tell you this gentleman did well. He actually went on a trial with maintenance tarlatamab. And a little interesting part about that, that trial allowed us to not have to put him in the hospital for the first dose and so that's been nice to see. Unfortunately, he relapsed in the brain. We treated that. And yesterday he came into clinic and he's starting a B7-H3 program, which we've seen some early results in the relapse setting.
This brings us to the end of the case, but I wanted to cover a few key clinical takeaways. The first is extensive-stage small cell lung cancer is often diagnosed in the hospital setting. Starting treatment in-house is a frequent challenge, but often can get patients better quickly and back to an outpatient setting. Second, platinum doublet immunotherapy is the current standard of care. Maintenance lurbinectedin, when approved, will be a new option for patients. The role of tarlatamab in the first-line extensive-stage setting is unclear, however many studies 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.
