Extensive Stage Small-Cell Lung Cancer - Episode 25
Naiyer A. Rizvi, MD: There are trials obviously ongoing in limited-stage small cell lung cancer with immunotherapy. Some of these patients can actually do very well with just chemotherapy and radiation, as Taofeek pointed out. Patients who have pre-existing paraneoplastic syndromes. You know, often, their paraneoplastic phenomena stay with them after treatment, and that can be a harbinger of a really good outcome. And so it’s going to be more challenging to develop immunotherapy for those limited-stage patients. What are your thoughts, Jamie? What do you know about the trial landscape or some of the trials you’ve had experience with in limited-stage disease?
Jamie E. Chaft, MD: We don’t institutionally have any of the trials for limited-stage open with chemo I/O [immuno-oncology]. But there are certainly many. I think there’s a combination of durva [durvalumab]—TREME [tremelimumab] being studied following chemoradiotherapy. I hear you about the subset of patients doing well. But that’s a bit small. And at 5 years, you’re still looking at about a 20% survival. So akin to stage III, unresectable non–small cell lung cancer, we need to do better.
I think the real question here is going to be whether the immunotherapy should follow chemoradiation, or if we should be looking at it with chemoradiation, looking at the maintenance studies, and in extensive stage and seeing that they’re negative, which was a surprise. But we should be investigating everything in this small but potentially curable patient population.
Naiyer A. Rizvi, MD: Yeah. Give twice-a-day radiation, which in itself can be pretty crippling for patients. So to give I/O, you know, presumably, there are safety studies that are being done. Maybe you want to talk about the concurrent approach and what your thoughts are?
Taofeek K. Owonikoko, MD, PhD: Yeah. There are a number of studies. One that I’m directly involved with is NRG-LU005. And that is using the approach of concurrent followed by maintenance atezolizumab. And there was actually a lot of discussion during the design of that trial with regard to the choice of radiation delivery. Ultimately the decision was made to leave it to the investigators to decide whether they want to use bid twice a day or single, daily fractionation. Because they want to make it real world. They don’t want to do a study that nobody can use at the end of the day.
That study is currently enrolling. It is a phase II/III trial that will compare concurrent chemoradiation plus atzeo [atezolizumab] followed by atezo [atezolizumab] maintenance to a standard arm of concurrent chemoradiation alone. It’s led by 1 of my colleagues at Emory University School of Medicine in Atlanta, Georgia, Dr Kristin Higgins.
And there is also the CheckMate 227 trial, which was a company-sponsored or supported trial by EORTC trial led by Dr Solange Peters. That is looking at maintenance, nivo [nivolumab]/ IPI [ipilimumab], following concurrent chemoradiation treatment. My knowledge of that study’s accrual is that it has been very slow compared with what they anticipated. And I think part of that was toxicity from the proceeding chemo after this patient that delayed there. I believe it’s a go on nivo [nivolumab]—IPI [ipilimumab].
And then there is the ADRIATIC study by Jamie, as I believe I told you before, which is a 3-arm trial that is also going to look at maintenance, question of durva [durvalumab], durva [durvalumab]—treme [tremelimumab], or placebo. That is also enrolling.
I think in the next couple of years we are going to have answers to these questions, whether the concurrent approach is the right thing to do or do we just wait—give the chemo RT [radiotherapy] first and then, like PACIFIC, go with consolidation treatment.
Ticiana Leal, MD: I think that in this setting, although we’ve been kind of jaded by the negative maintenance trials and the extensive-stage setting, remember that in that setting you’re using systemic agents alone. And how you’re kind of doing the PACIFIC-like regimen where you’ve got chemoradiation followed by a combination or immunotherapy. Again, trying to capitalize, is there a synergy there? Would it be different in that setting using these agents, in the maintenance setting when you have the combination chemoradiation radiation prior to that.
The second thing is, would that be better tolerated? If you’re sequencing these agents in a sicker population, is that also an advantage for small—cell lung cancer [SCLC] to do the immunotherapy following chemoradiation in that setting? I think it’s an interesting strategy. It’s a different question. It’s not truly just some maintenance. You know we’re really talking about consolidation in my mind, so I think it’s a little different, and I’m interested in seeing what the results are going to show.
Naiyer A. Rizvi, MD: I think for limited-stage patients, they’re unlike extensive stage, for whom maintenance was hard to deliver with only a median cycle of 1. I guess for consolidation, they’re unlikely to progress right away, so you’ll actually have time to deliver the drugs.
Jamie E. Chaft, MD: Yeah, that will be a really good setting to investigate some of our observations and toxicity in small cell, more extensive-stage experience, particularly in those patients who’ve had brain radiation and who had PCI [prophylactic cranial irradiation]. It’s going to be important to understand if the toxicity profile of I/O after PCI is different from the general population.
Naiyer A. Rizvi, MD: Do you see any usage of immunotherapy with chemo, or postchemoradiation and off-label in the community? Are people extrapolating the extensive stage?
Taofeek K. Owonikoko, MD, PhD: Actually I’ve not seen much of that. Perhaps in part because of insurance coverage. You know you if you can get insurance, then you can use it. I’m sure somebody must have thought of doing that.
Jamie E. Chaft, MD: These still tend to be the patients who don’t make it to academics.
Naiyer A. Rizvi, MD: But now these limited-staged patients, you know I’ve seen them pretty infrequently. It’s probably, I would say 10%, in my experience. It’s going to be harder to do these trials.
Jamie E. Chaft, MD: Yeah, they tend to stick in the community where the treatment of this disease hasn’t really changed in a long time, and they feel the urgency to get started quickly.
Transcript Edited for Clarity