The CASPIAN Versus IMpower133 Regimen

Transcript:

Naiyer A. Rizvi, MD: On to more recent data. Ticiana, you’re going to tell us about CASPIAN and what it looks like. Is it practice changing? How will you think about this new data in the context of IMpower133?

Ticiana Leal, MD: Talking about the CASPIAN data, this was recently presented at the plenary at the International Association for the Study of Lung Cancer 2019 World Conference on Lung Cancer [WCLC] by Luis Paz-Ares. And this is a phase III global study that had 3 arms. We saw the comparison of 2 arms presented at this point, and are still awaiting for the third arm. So this is a study that randomized patients to the standard arm, which would be the carboplatin-etoposide. It did allow cisplatin, which is different from the IMpower133.

The second arm was a combination with durvalumab, which is the PD-L1 [programmed death-ligand 1] inhibitor. And the third arm that we didn’t hear about included durvalumab plus tremelimumab, which was the CTLA4 inhibitor. This study included patients with PS [performance status] of 0 to 1. It did allow asymptomatic brain metastases. Interestingly in this study, PCI [prophylactic cranial irradiation] was not allowed in the experimental arm but was allowed in the control arm. The primary endpoint of this study was overall survival, and then there were secondary endpoints of progression-free survival [PFS], and overall response rate, as well as tolerability of the regimen.

What we saw were, in my opinion, results that really mirrored what we saw in IMpower133. We saw this is as a positive study with a primary endpoint of overall survival being met. And the difference was a 10.3 to about 13 months. So there was a similar difference in terms of improvement in outcome, in terms of overall survival. The PFS was similar between the 2 arms, but it didn’t meet statistical criteria to move on to actually look at it specifically for PFS. But nonetheless, we also saw that regarding the toxicities, there were no signals of increased toxicity, and the response rates were what we would expect. Overall what the study told me was, No. 1, there is something there in terms of chemotherapy in combination with immunotherapy. It’s reassuring that we’re seeing a very well-designed study that is once again confirming that, for a subset of patients with small-cell lung cancer, there is a benefit of adding immunotherapy to chemotherapy.

How does this change practice when we’ve been using the IMpower133 regimen? How this will overall rule out into clinical practice is the biggest challenge. There are a few differences there in terms of the regimen with the CASPIAN study allowing for every-4-week dosing versus every 3 weeks within IMpower133. And one of the things we were talking about was, is that good for patients and for clinicians? Are we more likely to use an every-4-week regimen, or do we feel that we need to monitor our patients closely and continue to see our patients every 3 weeks?

I’ll tell you, at our institution we kind of made the decision even when we saw that we could use ATEZO [atezolizumab] every 4 weeks, that we wanted to use it every 3 because we felt like we really wanted to monitor these patients closely, especially when we saw the maintenance studies negative and quickly—you know, quick progression, the every-3-week strategy seems to me clinically more appropriate for these patients, but I’m also interested in hearing from others.

Naiyer A. Rizvi, MD: Jamie?

Jamie E. Chaft, MD: That’s my practice pattern in this population or in any patients with non—small cell lung cancer who have aggressive or more symptomatic disease. Most of them need to be seen more frequently. And 3 weeks is kind of the outer limit of that frequency that I’m comfortable with. Although there certainly are the patients who live further away where travel is both a burden in terms of time, effort, and cost. I can see a place, particularly in rural communities, where the 4-week dosing is a huge advantage.

Naiyer A. Rizvi, MD: It’s expensive to park in New York City.

Jamie E. Chaft, MD: It is.

Naiyer A. Rizvi, MD: So let’s look at one regimen versus the other. Do you feel they’re fairly similar and interchangeable? What are your thoughts in terms of the data?

Jamie E. Chaft, MD: I think that they’d look very comparable. As was said, it’s reassuring to see this replicated because we always have doubts with just 1 study. The data were very comparable, and I think the unique feature of CASPIAN was that the control arm was treated very aggressively—as aggressively as could be. They were allowed to have up to 6 cycles of chemotherapy. They were allowed to have PCI, although the uptake was quite low, as is our national trend. But that was a really clean control arm with top-notch treatment, and still the combination outperformed, so it certainly reaffirms our new standard of care.

Naiyer A. Rizvi, MD: Taofeek?

Taofeek K. Owonikoko, MD, PhD: I’m of the same opinion that the results of the CT [computed tomography] scan are very important for the field, for 2 reasons. We had the IMpower133 where everybody looked and said, “They are positive, but I still want more.” And then we had the negative string of results from the maintenance and the relapse, which was a little difficult to question whether this category actually will work in small cell, to start with. And maybe the original result of the IMpower133 is questionable.

To have the CASPIAN trial come out, to replicate that result in a well-controlled, well-designed trial, is reassuring. This is a strategy that will help our patients. Unfortunately, at this point, we don’t know who those patients are. Finally, the small subset of patients who are really driving the survival advantage are key. When it comes to the schedule, I actually don’t have much concern in terms of the every-4-week schedule. Some of my patients with relapsed disease on nivolumab I treat every 4 weeks. I still do. As long as we have the data show that that’s comparable PK [pharmacokinetics] characteristics, between the every-3-week and every-4-week schedule, I would be comfortable doing either. But at least now we have a good platform to start building additional studies to identify subsets that will benefit. Or if you cannot, what other strategies can we add on to what we now have as our new platform, for their improvement?

Transcript Edited for Clarity