Charles Rudin, MD, PhD: At the 2019 World Conference on Lung Cancer, we heard the first results of the CASPIAN trial. This is designed fairly similarly to the IMpower133 trial, but with an important difference. Rather than a 2-arm trial, this was a 3-arm trial. It included the same or a very similar backbone of a platinum plus etoposide. The platinum agent could be either cisplatin or carboplatin in this trial. There were actually 2 investigational arms, 1 in which that backbone chemotherapy was augmented with the anti—PD-L1 [anti–programmed death-ligand 1] agent durvalumab and a third arm that included durvalumab and another immunotherapy, tremelimumab.

The results we heard about focused on only the control arm and the arm including durvalumab. The results of that trial showed an improved overall survival and improved progression-free survival in the patients who received the immunotherapy, durvalumab. The extent of benefit was actually very similar to the previous result in the IMpower133 trial with atezolizumab. I think together these 2 trials actually reinforce each other and help show the benefit of adding a PD-L1—directed therapy in the context of extensive-stage small cell lung cancer. So it was really nice to see a confirmatory trial in the same space come up with really the same result. That is a clear win for immunotherapy.

The third arm of the CASPIAN trial was not reported. We can’t read into that or say that means that it’s either positive or negative. It was not unblinded. The statistical design of the trial allowed more power to analyze the comparison with durvalumab alone. That was the first arm to actually cross a barrier for the Data Safety Monitoring Board to actually release those data. The data in the third arm remain blinded, and we’ll await those data at a future meeting.

One of the differences between the CASPIAN trial and the IMpower133 trial, which was interesting, was that the CASPIAN trial actually allowed patients with asymptomatic untreated brain metastases to go on trial without prior brain radiation. This is, I would say, consistent with what we would consider our standard of care. That is, if patients with extensive-stage disease have small asymptomatic brain metastases, we’ll start them on chemotherapy right away with the expectation that the lesions in the brain may also respond. In the CASPIAN trial, those patients were treated with chemotherapy on study, extending the potential application of these therapies to those patients. It was represented by 10% of the patients who were on that trial.

In my opinion, the data are practice changing. It has already changed our practice in the United States, where atezolizumab is currently approved for use. I think in the rest of the world, this is slowly becoming a standard of care. As the regulatory agencies look at this, we expect that there will be additional approvals.

Transcript Edited for Clarity