FDA's Approval of Opdivo and Yervoy Plus Chemo A Sign That the Field of NSCLC Treatment 'Moving Too Fast'

For the treatment of patients with non-small cell lung cancer, the field has seen one approval after the other, but for one expert this is a sign that things are moving too fast to be applied in a "rational trial strategy". 
BY Jessica Skarzynski
PUBLISHED June 24, 2020
In May, the lung cancer treatment landscape grew exponentially with an unprecedented number of Food and Drug Administration (FDA) approvals, one being the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) plus two cycles of chemotherapy for the treatment of metastatic or recurrent non-small cell lung cancer (NSCLC) in patients who have no EGFR or ALK genomic tumor mutations.

While this approval adds one more option to an already crowded field, Dr. Paul Paik, a medical oncologist at Memorial Sloan Kettering Cancer Center, explains that it is a sign that the field of NSCLC treatment is moving too fast. “Essentially, the field I think has moved too fast for us to be able to incorporate these new advances into any kind of rational trial strategy, because the trials take too much time,” said Paik in an interview with CURE®.

“By the time it's read out, this standard has shifted in terms of what we've been doing,” Paik explained. “And that's not necessarily a bad thing. It just reflects that there's a great deal of enthusiasm and activity in the space, but it does make it difficult to rationally figure out what to do for a particular patient.”

One benefit to this approval, Paik noted, was that it could potentially offer patients who are sensitive to chemotherapy a treatment that is less chemo-intensive while still maintaining safety and efficacy.

CURE: What was your initial reaction to the approval of Opdivo and Yervoy plus chemo as a frontline therapy for NSCLC with no EGFR or ALK mutations?

Paik: That one was a little more muted, I would have to say. And the reason why is because sort of like what we've seen in the outset, there are a lot of positive first-line trials now that use immunotherapy as part of the regimen, either as a single agent in combination with another checkpoint inhibitor or with chemotherapy, so many of these trials have read out and many of these have gotten FDA approved. And they are all using as their control arms, standard chemotherapy and not each other. And so, it makes it even more confusing to try to figure out the relative efficacy against everything else.

Essentially, the field I think has moved too fast for us to be able to incorporate these new advances into any kind of rational trial strategy, because the trials take too much time. By the time it's read out, this standard has shifted in terms of what we've been doing. And that's not necessarily a bad thing. It just reflects that there's a great deal of enthusiasm and activity in the space, but it does make it difficult to rationally figure out what to do for a particular patient.

… My attitude to this was, it's another immunotherapy frontline regiment that's approved. That's great, but it adds to the confusion as to what we're supposed to do. And while formally, you could say we just need to run a very large randomized trial, with lots of these arms there, at this point, I don't know if that's going to happen. First of all, because it's going to have to probably happen with the cooperative groups, and it would have to be quite large. So, we'll see whether or not there is any enthusiasm to get that done.

What does this approval mean for patients?
Again, I think it may offer a little bit of additional flexibility to tailor the regimens.

One example in terms of a niche where it may fall, would be for patients who have squamous cell lung cancer, where the standard of care would be (the) Keynote-407 (trial therapy) which is carboplatin, ataxane plus pembrolizumab, where the triplet regimen is given for four cycles, and then there's maintenance pembrolizumab thereafter.

It could be that, maybe for a patient who we think is not going to tolerate as much chemo, for example, four cycles, that this may be another option to give less chemo, but still being assured based on the data that the efficacy is going to be there. Because you could do that with the Keynote-407 regimen. But technically, we don't know if four versus two cycles is important. It probably is not so important, but technically we don't know. So that is a potential option that's there.

It just speaks to the fact that, especially I think with these immunotherapy-based regimens, there's a lot of patient-specific thought that goes into what to provide, not just from a biomarker standpoint, (like) what the PD-L1 expression level is or what the histology is, but also in terms of how well they're doing, how sick are they from their cancer, and what their own preferences are in terms of exposure to chemotherapy, for example. So, you know, it adds, potentially to that conversation.

What does this approval mean in the broader sense of how it impacts the field of lung cancer treatment?
 
I think in the broader sense it provides further inertia for us to get our act together on the academic side and filter all this data in a way that's comprehensible, but also understandable to our patients to really figure out what the best option is.

Having all of these approvals is great, but if patients are having a lot of difficulty, and the providers themselves, are having a lot of difficulty figuring out what to do, that's not a great situation to be in. And so, I think we need to help clarify what should be done with these pathways, but that's not going to be easy. And this is again, going to require randomized trials to be able to do that, and that's just going to require a great deal of effort.


See our breaking news coverage on the approval of the combination of Opdivo and Yervoy plus chemo in the frontline setting for NSCLC here.
 
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