Naiyer A. Rizvi, MD: Here’s a curveball question. What do you do in terms of first-line therapy for a mixed small cell/non—small cell histology patient?

Taofeek K. Owonikoko, MD, PhD: A real curveball. The way I approach situations like that is thinking about what is likely to do the patient the greatest harm within the shortest period of time. That is small cell. I tend to treat those patients, and this is consistent with most of our guideline recommendations as well, as if they had pure small cell lung cancer [SCLC] to start with. I go with the small cell strategy and then see how well they respond, and if I have to adjust my strategy after that, I’m not going to compromise that initial treatment approach for the patient.

Naiyer A. Rizvi, MD: Ticiana, do you want to let us know your thoughts about whether you use chest RT [radiotherapy] in responders or PCI [prophylactic cranial irritation] in responders? Is that something you do?

Ticiana Leal, MD: In extensive-stage small cell lung cancer, I think increasingly at our institution we have that multidisciplinary discussion with our radiation oncology team. And we’ve used PCI less and less frequently on a routine basis for patients with extensive-stage small cell lung cancer. And this is mainly based on the Japanese data with the phase III trial that really show that perhaps increased and close monitoring with adequate MRI [magnetic resonance imaging] may be just as good as PCI with less toxicity. That’s kind of our approach for patients. Obviously, we do have that discussion among ourselves and with the patient.

I think the other thing, too, is the role of PCI now that we’re using combination of chemotherapy and immunotherapy in extensive-stage small cell lung cancer. In the IMpower133 study, which we’ll talk about later, there was just a small number of patients that actually got PCI, and there wasn’t really a signal of increased toxicity there. But we can’t really comment on if there was any efficacy difference there. And in the CASPIAN study, which we’ll talk about later as well, PCI was actually not allowed on the experimental arm with the durvalumab combination. So I think we’ll still have to find out more about how does PCI fit in to the era of using combination of chemotherapy-immunotherapy. But as of now, I think I use it in selected patients.

Naiyer A. Rizvi, MD: And chest RT, Jamie?

Jamie E. Chaft, MD: Well, we know that the data on chest RT didn’t show an overall survival [OS] advantage, although there are considerations for patients with extensive stage but still relatively limited stage, particularly those with residual disease in the chest where they are at great risk of morbidity from progression in that disease. I do discuss these patients with the radiation oncologist, and I use chest RT in select patients. But doing more extensive consolidative RT, I don’t think we have the data.

Ticiana Leal, MD: I’m interested in what that means in the era of immunotherapy [I/O]. As we talk about how immunotherapy and radiation can synergize, is that something that we can use as a strategy in small cell lung cancer, especially in patients who are responders? Is there going to be an efficacy or synergy there? I think that’s something that perhaps needs to be further explored.

Taofeek K. Owonikoko, MD, PhD: Yeah, I think that’s actually a good consideration in terms of how we integrate thoracic radiation therapy following the initial induction chemotherapy-immunotherapy as we continually adopt our practice toward what the data are showing us. I think after seeing the results of the CREST trial, I’m still actually very struck at how much adoption that study has seen in the community. At Winship Cancer Institute of Emory University in Atlanta, Georgia, for instance, our practice pattern is not to offer thoracic radiation therapy as a standard approach to our patients. We actually don’t view that as something that is proven by the study because the primary endpoint of the study was to show superiority of that in terms of median overall survival, and it did not. While there was the possible signal of 18-month or 24-month overall survival advantage, that’s really a very small subset of patients who are enrolled in that study.

Not being the primary endpoint, the argument is always, if you had a positive study but then you had a subset analysis that was negative, are you now going to do it because of the subset analysis? I think the corollary should be true as well, that if the primary endpoint of a study is not met, we should keep digging. Potentially, there could be some patient that will benefit from this. We just don’t know who they are.

The follow-up analysis was from our European colleagues, who looked at a subset of patients on the CREST trial to try to understand who benefited and who did not. It was patients who actually had good response and especially those with limited number of sites of metastatic involvement of 3 or less. But prospective study would help us decide whether this is the right strategy now that we’re going to have a lot of our patients on the immunotherapy.

Jamie E. Chaft, MD: The immunotherapy is really what changes that, because historically we did nothing. I think the uptake was a result of us feeling as if we had something more to offer, particularly in those with just limited involvement.

Transcript Edited for Clarity