'Easy' to Navigate Recent Flurry of Drug Approvals in NSCLC Since Most Are 'Just Another Option'

Most of the data from the recent approvals of several non-small cell lung cancer drugs don’t distinguish themselves regarding efficacy or safety to what was already available before the flurry of approvals in May, according to Dr. Timothy Burns.

Both patients with cancer and oncologists will have a relatively easy time determining which of the countless recent drug approvals in the non-small cell lung cancer space are best for patients, according to Dr. Timothy Burns.

“Most of the recent approvals, with some notable exceptions, are just another option or another kind of similar option,” Burns, a medical oncologist at UPMC Hillman Cancer Center, said in a recent interview with CURE®. “They don't distinguish themselves in terms of either increased efficacy, or tolerability, compared to what we had in April.”

Burns discussed the possible rationale behind the Food and Drug Administration’s approval of seven non-small lung cancer drugs in May. He also offered insight into why the FDA may not have approved a certain therapy, even though results of the ADUARA trial were promising for the use of Tagrisso (osimertinib), as well as how everyone can decipher which new treatment options are best for patients.

CURE: Seven therapies were approved by the FDA in the non-small cell lung cancer space in May. You mentioned that data from the ADUARA trial were promising, yet the therapy has not been approved. Why might that be the case?

Burns: There's been a lot of discussion in the field about this because this was a trial that was stopped early by the external data safety monitoring board because it was unethical to continue people on the placebo. They made the trial cross all the patients over to Tagrisso. Based on that and based on the data that was presented at ASCO … it's a little confusing that the FDA has not approved this yet. I will say that with previous EGFR tyrosine kinase inhibitors, what they found when they used them in this setting, is it delayed recurrence, but then once you stop the drug, the patients recurred. Again, with this trial, this was stopped before it was planned (to stop). They had to unblind the data at this point. But the difference that we see with this particular drug … is an 83% reduction (which) is much greater than we ever saw with the older generation drugs which were on the order of 30 to 40% (reduction). Although a lot of us in the field would like the data that comes out in the next three or four years, I think we're all willing to accept this as a standard of care now, and so we're just waiting for the FDA to approve it or at least become part of the (National Comprehensive Cancer Network) guidelines, which technically if it's on the NCCN guidelines it will get covered by insurances.

You mentioned that it’s rather rare to see so many approvals in one type of cancer in a month. How desperately needed were these treatments?

The approvals that came out, and that's kind of the confusing part, is that in first line therapy for non-small cell lung cancer, not talking about driver mutations, you do molecular testing. And if you have a molecular alteration, generally (the patient is) going to get targeted therapy. So, the other group of patients, which is about 50 to 60% … will get chemotherapy. So, then what are your options? Before May, either squamous or non-squamous either had pembrolizumab alone and those that had high PD-L1, although it was also approved for anyone who had any PD-L1 positivity, although the way we think about it in oncology is the patients who have benefited were the greater than 50%, and so that was an option. For the rest of the patients, and even for those over 50%, who also had chemotherapy plus immunotherapy, and there were several approved regimens, either involving Keytruda or involving atezolizumab with bevacizumab. So, you had an option of immunotherapy alone, chemotherapy plus immunotherapy, and then you also had the approval of nivolumab plus ipilimumab prior to this. What got reported, and what was kind of surprising, was this study where essentially it was “chemo-lite”, you had nivolumab and ipilimumab and you gave two cycles of chemotherapy versus four and no immunotherapy. This was a positive study because it was better than chemotherapy. The issue with this is nivolumab and ipilimumab was also better. It would have been surprising if it was not better than chemotherapy alone because we already knew that nivolumab and ipilimumab was better than chemotherapy alone.

So the question you ask yourself is, what was the area of need that they were trying to address in the patients that you can't give chemo or you don't want to give chemo? We had pembrolizumab approved and then we just recently had atezolizumab approved. Or, you had nivolumab and ipilimumab. It's difficult to see a patient that if you're going to give chemo, you're only going to give two (cycles) and if you're not going to give chemo then what's the benefit of this? I'm not quite sure what was the rationale to design this study. It's kind of the worst of both worlds, I guess. Or if you're going to avoid chemo, then avoid chemo and if you're going to give chemo then I'm not sure that giving two (cycles) versus four (cycles) makes a big clinical difference. But it was a positive study and the FDA based on this decided to approve it. I don't see a lot of uptake of this regimen.

When breaking down all the approvals, how does one get through all the information regarding what is best for patients?

I think in some ways, it's easy because most of these approvals aren't going to change anything, right? Most of the recent approvals, with some notable exceptions, are just another option or another kind of similar option. They don't distinguish themselves in terms of either increased efficacy, or tolerability, compared to what we had in April.

When you're going to treat someone, especially in the metastatic setting, the goal is to extend life but, you're not going to do something that's hurting the patient and you want something that works. So, these approvals say, single agent atezolizumab which was maybe equivalent to pembrolizumab, or nivolumab and ipilimumab plus chemo doesn't really change our practice. So, it's not something that is going to change what we would do. Essentially the paradigm that we had in April is the same paradigm we have today.

Now, there are some notable exceptions. If you have a MET mutation, we now have an FDA approved therapy and I am starting patients on (Tabrecta) and … I think that's practice-changing in the adjuvant setting. I actually had a discussion with a patient with an EGFR mutation last week, and we're trying to get her Tagrisso and I said that I expect that the FDA or the NCCN will put this on the guidelines. We had this discussion a few months ago and I said I couldn’t tell her whether it was going to delay or cure, but that the data looks very promising. Those are two things that have changed since April to today. But another monotherapy in first line, or another combination that it's not even clear if the nivolumab and ipilimumab plus chemo is any better than nivolumab and ipilimumab, right? So, that's one question that's not answered ... but they're not really practice chanting at this point.