番茄社区

The phase III ADRIATIC trial showed that adding consolidation treatment with durvalumab (Imfinzi) following concurrent chemoradiotherapy significantly improved progression-free and overall survival in patients with limited-stage small cell lung cancer (SCLC), as reported at the American Society of Clinical Oncology (ASCO) annual meeting.

番茄社区 brought together three expert leaders in the field: Moderator Roy Herbst, MD, PhD, is joined by Anne Chiang, MD, PhD, and Sarah Goldberg, MD, MPH, all of Yale Cancer Center in New Haven, Connecticut, for a roundtable discussion. This first of four exclusive episodes focuses on ADRIATIC.

Following is a transcript of their remarks:

Herbst: Hello, I'm Dr. Roy Herbst, deputy director of the Yale Cancer Center, chief of medical oncology, and the assistant dean for translational research. I'm really excited to be here at ASCO with a panel of experts to discuss new advances in lung cancer. In fact, I have two of my colleagues from Yale who will now introduce themselves. Anne?

Chiang: Hi. Great to be here today. I'm Anne Chiang. I'm the Associate Cancer Center director for clinical initiatives and I lead our small cell program.

Herbst: Great. And Sarah?

Goldberg: I'm Sarah Goldberg. I'm a thoracic oncologist and the chief of thoracic oncology at Yale. It's great to be here.

Herbst: Great. What an amazing meeting. We're in the final stages, but there's been so many presentations on lung cancer. In fact, Sarah, I know you were involved in the program committee this year. You want to just give us an overview of just some of the areas that we might be talking about today?

Goldberg: Absolutely. I agree. This has been a great ASCO. We're not even done yet, but there's already been so many really exciting findings in a few different areas, which is really great. We've seen some really nice data in EGFR-mutant lung cancer in the locally advanced space. I think some of the updates that we've seen for ALK-positive lung cancer, metastatic ALK-positive lung cancer are really, really exciting and impactful. We've seen great data in small cell, antibody drug conjugates are really up and coming and we've seen some interesting and important studies there. So really the gamut, oh, early-stage as well, resectable lung cancer, so there's been a lot of really exciting updates and advances that we've seen at ASCO this year.

Herbst: Absolutely. I think I've been a member of ASCO since 1997 and I can't remember a year with more exciting lung cancer presentations, a plenary with three programs. There's even one on palliative care. And what do you think about that, Anne?

Chiang: The plenary was so exciting. Two positive lung studies, two standing ovations, palliative care looking at telehealth use. I think that's sort of important to show because we do use telehealth and we want it to keep getting reimbursed, so that's an important thing.

Herbst: OK, let's dive right in. So we're going to talk about several different topics. Let's start with small cell lung cancer because we always used to leave small cell lung cancer for the end of the meeting, but now there's so much exciting data and there was a recent approval before ASCO and then the ADRIATIC trial. Tell us a little bit about what's hot, Anne.

Chiang: This is such an exciting time for small cell. The ADRIATIC trial, which was presented at the plenary actually, so that was for patients with limited-stage disease and then randomized them to either immunotherapy versus not, and that actually showed a 22 month improvement in overall survival. That is the first breakthrough for limited-stage in five decades. So that's an amazing thing for our patients, improving their survival and it's going to be practice changing. I've gotten questions about that already.

Herbst: Were there any toxicities associated with it?

Chiang: The toxicities were very comparable between both of the arms. The pneumonitis was about the same, so there weren't any more toxicities in the immunotherapy arm.

Herbst: What do you think, Sarah? Does it become standard of care?

Goldberg: Absolutely. We already do this for non-small cell lung cancer for locally advanced disease, unresectable locally advanced disease, the Pacific regimen where you give chemoradiation and then durvalumab, and I think it's just now a natural extension after we see this data that we're going to now do this for limited-stage small cell. We'll give our chemoradiation and then go into immune therapy. But like Anne said, we didn't have this before. For our non-small cell patients we were doing it, but for small cell we weren't. And now I think this is clear data that it's what we should be offering our patients.

Herbst: One of the questions that was asked in the plenary was, do you still then need prophylactic cranial irradiation [PCI] with the potential cognitive side effects? What do you think about that?

Chiang: I think that the use of PCI is going down. I mean, we do have clinical trials that are going to help us understand whether that is something that we should recommend, but I think with better [magnetic resonance] surveillance, we always have that conversation with our patients, but more and more patients are really not willing to do it, and I think our radiation oncologists are also on board. It's just the use of that, it's going to go down. So we'll be able to understand that with subset analysis, but stay tuned.

Herbst: And how common is limited small cell lung cancer in your opinion?

Chiang: It's about 15% of what we see. So if a good portion of our patients do have limited-stage, I think that one of the lessons here is that we need to push our screening. If we can detect these patients earlier, we can give them those benefits.

Herbst: Absolutely. And before we go off the small cell lung topic, there was a recent approval of tarlatamab [Imdelltra]?

Chiang: Yes.

Herbst: How's that and how will that get moved into all of this?

Chiang: Oh, this is super exciting. It's a bispecific antibody that targets DLL3 and CD3, it's a T-cell engager. This is important because small cell is really, if you look at the tumors -- and we have nice pictures of this -- it's an immune desert. There are very little T cells. PD-L1 expression is about 5% in small cell, and when you treat, then you have lots of T cells coming in, and I think this is the bispecific approach, or some trispecifics also out there, are getting the T cells to where they need to be.

Why are we so excited about this drug? It has a 40% response rate. It has a 70% disease control rate, and the overall survival or the duration of response is greater than 6 months. At 6 months, there's about 60% of the patients still having an ongoing response. This is a game changer.

And the issue around it is that we're going to have to learn how to use it because we do have cytokine release syndrome, the first couple of doses. So we're going to have to initially admit our patients for observation afterwards, make sure that we educate our patients if they have fever, if they're not feeling well, they really have to come in right away and then we can treat them with [dexamethasone], we can treat them with [tocilizumab] and take care of it. It's manageable.

Herbst: So everyone has to get admitted after they get the drug?

Chiang: Right now, that's the way that the approval comes. That being said, we participated in the 8-hour monitoring cohort and some of the newer trials are just outpatient, so.

Herbst: We're going to need more beds.

Goldberg: I was thinking the same thing.

Herbst: What is this cytokine release syndrome?

Goldberg: Yeah, it basically is the immune system is overreacting to the drug and you get fevers and get hypotension. People can get pretty sick and that's why you're monitored initially. So it's something that hopefully with these new studies and understanding it better, maybe we can do it outpatient for reliable patients. I would hope so, because I agree, the bed situation is going to be challenging.

One other thing maybe I'll say about tarlatamab that we saw at ASCO this year is they looked at patients on this phase I study who had brain metastases and they did just as well. So that's really important. A lot of patients with small cell lung cancer have brain metastases. The trial, I think, did require radiation before going on, so it's not untreated brain metastases, but those patients often just don't do well when they have brain metastases, is kind of a marker of sometimes can be really limited amount of time, but these patients did really well. So I'm excited about this drug and now it's approved so it's available. We can start using it hopefully soon.

Chiang: It's an area of unmet need, the brain mets [metastases]. Like you said, that was really exciting, really important to know that those were treated brain mets, so the patients who had treated brain mets did as well. There's no issues there, but it didn't show us that there's intracranial activity.

Herbst: That's right. Very good. Well, I think we'll move on. Small cell, not so small anymore, huh?

Chiang: Yeah, exactly.

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