The CASPIAN Trial in Extensive-Stage SCLC



Jacob Sands, MD: We saw, at [the International Association for the Study of Lung Cancer] World Conference on Lung Cancer this year [2019], a presentation of the CASPIAN data. Two of the arms were presented. The durvalumab-tremelimumab was not mature. Those 2 arms are platinum-etoposide for 4 to 6 cycles versus platinum-etoposide for 4 cycles with durvalumab added in, and then durvalumab maintenance after that. What we see from the study results are really a validation of what we saw from the IMpower133 data. We see modest improvement in progression-free survival [PFS] and overall survival [OS], but we do see an increase in that tail. Now, I’ll say that the median PFS and OS were both statistically significant—it was considered a positive study. But the real results I think we’re seeing are in that tail—an increase in the tail, and the durable responses out beyond a year.

Given the prior IMpower133 data, and I would say the use of atezolizumab as the standard of care now, the addition of the CASPIAN data isn’t necessarily a new paradigm. But I think it is a new option, and I would anticipate this being approved just like the IMpower133 data that led to the approval of atezolizumab. People will have the opportunity to choose whether they want to give atezolizumab or durvalumab in that frontline setting. But I would consider that a continuation of what has already become the standard of care.

Fortunately, the checkpoint inhibitors are generally very well tolerated. The adverse-effect profile is different from what we see with chemotherapy, so it actually pairs fairly nicely and doesn’t really tend to increase the difficulty of getting through treatment.

As far as the toxicities, though, we do see some patients who really end up having a hard time. Although the majority of patients really tend to cruise through without much difficulty or much in terms of adverse effects that show up, we do sometimes see people with significant diarrhea or rash; and really, the big 1 actually is pneumonitis. So it’s important to recognize these possible toxicities, and when you see somebody who really is having more substantial symptoms, to recognize that early. Now, with each as initial therapy, it is important to try to treat that toxicity.

Of all of them, pneumonitis is probably the most important to recognize early. Most of these people with small cell lung cancer are people with some limited lung function already from a significant smoking history or sometimes significant COPD [chronic obstructive pulmonary disease]. Being able to recognize more cough—sometimes we’ll see these inflammatory changes on their CT [computed tomography] scans—can sometimes be hard because people often have a cough and also already have respiratory symptoms intermittently.

Sometimes I see people for whom there’s something that maybe I’m a little concerned about. But then, as we talk about things more, I feel more comfortable, and we go ahead and proceed with treatment. And other times I’ve seen people for whom things are kind of lining up in a way that makes me a little more concerned. There have been times I’ve held treatment. Many times, when patients do have these adverse effects and you treat through them, as long as the adverse effects haven’t really been substantial and they really fully recover from them, then reinitiating therapy doesn’t necessarily cause that full adverse-effect profile as it did before. It’s important to take this case by case, individual by individual, and to just monitor closely for these.

Transcript Edited for Clarity

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