Taofeek K. Owonikoko, MD, PhD: Dr Sands, walk us through the current standard-of-care approach for patients with newly diagnosed extensive-stage disease. What are the typical components of the regimen that you use, [what is] your insight into the mechanism of action, and why do you choose what you use?

Jacob Sands, MD: There are 2 standard-of-care options. And I’d say there are 2 trials those have come from: They are carboplatin-etoposide [and] atezolizumab as a combination, and platinum-etoposide and durvalumab as another option. Those are both FDA approved, and I’d say widely used, and [clinicians] tend to use one or the other. But they’re both valid. They’re both usable. In some centers, they’ll kind of interchange [them] but I think widely, [clinicians] tend to use one of those. These are both PD-L1 inhibitors. I often describe these as something that essentially, blocks the [identification] badge that these tumor cells are using to hide from the immune system. By blocking that, the immune system better recognizes them and treats them. I think patients often like hearing that these are not toxins in the way that chemotherapy is a toxin. But they actually help the immune system be the reason for killing the cancer cells. And that’s an appealing mechanism.

They’ve also been really revolutionary in the tail of those curves and in those responses. I described it a little bit in that overview, but I’ll just highlight: With atezolizumab, it was carboplatin in the trial, and that’s for 4 cycles of carboplatin/etoposide. And in the CASPIAN trial with durvalumab, it was either cisplatin or carboplatin, and etoposide. But again, 4 cycles, and then continuing the immunotherapy from there. I’ll also point out that both atezolizumab and durvalumab can each be given every 4 weeks. Sometimes that’s something I highlight for patients who are being treated somewhere else and have come for a second opinion. In that maintenance setting, the every-3-week dose can then be increased to every 4 weeks, which is a little bit better of a schedule, especially in that time frame when [patients] are doing a bit better…. The CASPIAN trial, I believe, did not require all brain mets [metastases] to be entirely treated, which I’d really like to support. I really advocate for this being done more in our trials; particularly these really small brain mets are not something we would necessarily withhold the initial systemic therapy for, but it allows us to give the systemic therapy as we’ve done with platinum-etoposide, and that’d be something that we can later go back to. So that’s a bit of an overview on those 2; I call them both standard-of-care options.

Taofeek K. Owonikoko, MD, PhD: Thank you. Dr Leventakos, now that we know what the standard-of-care options are, are there specific clinical factors that you put into consideration when you choose any one of these regimens for your patient?

Konstantinos Leventakos, MD, PhD: Yes, before we touch on that, I have a comment, based on the case that was presented; it is very important that the discussion with the patient really reflects these good responses. Because we know that our [patients with lung cancer] especially might have a lot of guilt for the diagnosis. And it is important to let them know that this chemotherapy with immunotherapy will probably make them feel better and live longer. I have seen it many times going into challenging discussions, trying to, of course, have certain decision-making but I’m trying to make it evident that it will be a beneficial treatment for them. And the other thing is that for most of the chemotherapies as oncologists, we really look at the performance status as something that will make us decide whether we will give chemotherapy. I think small cell [lung cancer] is one of the best examples where I have given chemotherapy with immunotherapy in patients who did not have the usually acceptable performance status because we know of these dramatic changes. When it comes to deciding, in my experience, the 2 regimens that we use have a lot of similarities [but also] some huge differences that make me prefer one over the other. Sometimes the availability of giving cisplatin to someone who starts with hemocytopenia because we know sometimes patients might start with hemocytopenia because of bone marrow involvement might make me go to CASPIAN because it had the cisplatin regimen available. But otherwise, I do not have a lot of other reasons to choose one over the other.

Taofeek K. Owonikoko, MD, PhD: When you think about the stage at which the patient is presenting, what’s your approach between limited stage vs extensive stage? For which regimen would you use carboplatin or cisplatin immunotherapy? Can you share your insights on that?

Konstantinos Leventakos, MD, PhD: …I’m going back to the stages and the basics that we treated stages differently. When it comes to limited-stage [disease], we definitely do not have a lot of data for the incorporation of immunotherapy right now apart from clinical trials. At Mayo Clinic, we have some of these clinical trials. And we always prefer a clinical trial of standard treatment, of course. But in the case that a clinical trial is not available, the standard treatment for limited stages would be concurrent chemotherapy radiation, usually cisplatin with etoposide with our radiation oncology colleagues leading. Many times, again, we might start with 1 cycle of chemotherapy and catch up with radiation in the following cycle or as soon as possible. I would like to mention that sometimes we have the case that you very nicely described as a resected nodule that is small cell. And in that case, irrespective of the size, we would do some adjuvant cisplatin, preferably with etoposide. So again, going back to the basics, I think staging and appropriate treatment per stage is the most important thing. And we all celebrate the advances that came with immunotherapy, we want to see positive results from the trial so that we can give this benefit to the patients with limited stage.

Taofeek K. Owonikoko, MD, PhD: I think listening to all of you, it’s definitely no surprise that we have quite a very uniform approach to treating [patients with] this very difficult disease. From my standpoint, I follow more or less the same approach that you’ve all described. One area that we haven’t touched upon, that I just want to also bring up, is the use of radiation in this patient outside of the limited-stage setting. I would say before the advent of immunotherapy in this space, 2 areas that we really concentrated on were prophylactic cranial irradiation [PCI] as well as consolidation thoracic radiation. I think the CASPIAN trial, as Dr Sands mentioned, actually helped us to get away from having to treat patients with asymptomatic brain mets and the follow-up, and the consequence of that is for a lot of these patients we can avoid PCI as long as you can closely monitor the brain. The second is the consolidation thoracic radiation, which I’ve never been a frequent user of; given the design of IMpower133 and CASPIAN did not allow for thoracic radiation to be given. I will say my own practice is not to consider thoracic radiation unless I have a patient with symptomatic disease that requires additional treatment on top of chemo-immunotherapy. I don’t know whether any of you have experienced situations where you are forced to offer consolidation thoracic radiation to any of your patients without symptoms.

Konstantinos Leventakos, MD, PhD: I think all the data that we have are getting a little old and they are before the end of the immunotherapy right now. But again, going back to clinical trials that we have ongoing is looking into consolidated radiation while the patients are on immunotherapy. And I think that the data from this trial would be very important for us to understand: first of all the safety and, second, how much it helps patients. But it is not something that we do very extensively outside of the clinical trials.

Jacob Sands, MD: I do think it’s an important consideration in select patients. And to be very clear, anytime I’m considering that, I’m saying, “Hey, we’re kind of going outside the box on this one.” But in someone who primarily had extremely bulky central disease that had a nice response to therapy, the radiation field of consolidation is not going to end up being one that I’m particularly concerned about. It’s something to consider as a 1-off. It’s challenging, though, because we see 10% or more of these patients who have just got the immunotherapy and ongoing years out on the curves still have disease control, and looking back radiating those individuals would not have been helpful for someone who has that kind of durability from chemo-immunotherapy. But to the question that Dr Chiang answered, we can’t predict who’s going to end up having a recurrence or having growth progression. But in someone where I’m particularly concerned about their progression in the chest, and I have an opportunity, I would sometimes consider that as an outside-the-box, individualized kind of consideration.

Taofeek K. Owonikoko, MD, PhD: I think that’s an important consideration for all of us to be aware of and, depending on the patient’s unique situation, to bring that discussion up with the patient.

Dr Chiang, let me come back to you. One of the differences between the trials as we try to figure out what we do for a patient is this issue of shortage of chemotherapy cisplatin and carboplatin. We know that for IMpower133, carboplatin was the only chemotherapy; for the CASPIAN trial, they allowed both. How has the current shortage of cisplatin and carboplatin impacted your approach to the use of chemo- immunotherapy in this patient population?

Anne Chiang, MD, PhD: This is a real national emergency for our patients, and there are a lot of patients across the nation who are not getting the appropriate treatment. I think that the fact that the CASPIAN trial allowed both cisplatin and carboplatin put my heart a little bit at ease in terms of being able to use that. I think even if we didn’t have that data, we are still using cisplatin if we don’t have carboplatin. It’s nice to have those data, though. We were getting short of carbo [carboplatin], and then we were starting to use cis [cisplatin]. Now we’re short of cis, we’re starting to use some carbo. But I think overall, this is, unfortunately, something that we hopefully can get as a system our hands around so that our patients don’t have to feel that.

Taofeek K. Owonikoko, MD, PhD: Has anyone had to switch midcycle or midtreatment between carbo and cis in the beginning to choose one or the other? [Perhaps you started a patient] on carboplatin for the first 2 cycles, and then went on to cis or the other way around?

Anne Chiang, MD, PhD: I’ve done that if they had hearing issues, and then we had to stop the cis. Generally, the carbo is pretty well tolerated, but we have had issues with myelosuppression that made us go to the cisplatin.

Jacob Sands, MD: …With the shortage, and having to switch from carboplatin to cisplatin, I hope we’re not really faced with having to do that. There are certainly patients who I think would tolerate it, and historically, cisplatin was more difficult to tolerate. As you pointed out earlier, nausea and vomiting are now pretty well controlled with our antiemetics. So cisplatin isn’t nearly the problem it was historically. That being said, I don’t want to be faced with having to make that decision based on drug shortages.

Taofeek K. Owonikoko, MD, PhD:Are there unique clinical or biological features that you look for when you select between a durva [durvalumab]-containing regimen vs an atezo [atezolizumab]-containing regimen?

Jacob Sands, MD: I highlighted the differences in the way the trials were done. And again, I’ll just say that trials that allow for untreated brain mets, if they’re asymptomatic, I think this is important. But the practice of utilizing these drugs, I see them as fairly comparable. I recognize the comfort in someone who’s getting cisplatin, given that the trials with durvalumab allowed for cisplatin. I don’t foresee there being a real difference in the drugs in that setting, and I don’t feel strongly either way. There are some centers that use one of these in all of their patients and others that use the other in all of their patients. And then some centers, it sounds like, Dr Chiang, where you use both, depending on the patients. And I think these are all valid. I think the most important thing is that patients are getting this. And this is also going back to equitable care and where we’re talking about seeing that the real-world data are the same, but the real-world data are the same in [patients] who got it…. We need to find a way for all patients to have access to this care in the first-line setting, whether they’re getting atezolizumab or durvalumab or other drugs that end up ultimately improving in the process. Serplulimab was impressive in the presentation. So we’ll see, but [we must make] sure that everyone really gets access to the standard first-line care.

Transcript edited for clarity.