Immune checkpoint inhibitors are now becoming approved and commercially available for patients with previously treated advanced NSCLC. Dr. Eddie Garon, medical oncologist at UCLA, summarizes key data and explains their current role in treatment.
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So, the initial studies of checkpoint inhibitors have been in patients who have been previously treated, and one of the reasons for that is that has been, typically, a difficult clinical scenario. We have been able to be somewhat effective, certainly with chemotherapy, and there are many people who do quite well for a long period of time with chemotherapy in the front-line setting. But, unfortunately, that’s much less common in the second-line setting — most patients, for instance, with mutations in EGFR or ALK now are receiving inhibitors of those in the front-line setting, so when you take, for instance, patients who do not have mutations in those genes and look at them in a second-line setting, we generally have anticipated that about 10% of them would have, what we would call, a clinical response to chemotherapy, and that that response is generally not of the sort of duration we would want. So, it was an excellent opportunity when the checkpoint inhibitors became available, to test whether or not they could lead to superior outcomes than, for instance, docetaxel or Taxotere. Taxotere has been a standard drug that has been used for many years in this setting, and can be effective, but is less effective than we would want, and is associated, certainly, with some toxicity.
So, the phase 1 study looking at Opdivo, for instance, looked at that group of patients, and then — I was involved with a very large phase 1 study where we actually treated, it was 495 patients total, and about 400 of those patients were previously treated, so they had received prior therapy, and there you saw somewhere near 1 in 5 patients responding to the drug, and when they responded, they responded for a long period of time. But, that data, although a large data set, was not compared to standard therapy, so it’s important to evaluate what would happen if you compared a checkpoint inhibitor, for instance, to standard therapy, because that’s what you’re going to have to be deciding in the clinic, is whether or not you want to use one of these kinds of drugs or if you want to use a drug like Taxotere.
So, the first data sets, now, are available in that setting, and the first one to read out was the CheckMate 017 study, this was of the drug Opdivo, and this took patients with squamous cell carcinoma, one type of non-small cell lung cancer, and randomized them to receive either Opdivo or Taxotere. The results were, from a clinical trial perspective, very clear — that patients benefitted if they received Opdivo. Of course, not every patient benefitted, but when you looked at the outcomes and how the patients responded to the drug, how long people were able to stay on the drug, how long people survived, clearly it was in favor of Opdivo, and Opdivo is now approved in squamous cell carcinoma of the lung.
CheckMate 057 looked at non-squamous, non-small cell lung cancer — there, again, compared to Taxotere. It, again, led to improvements in clinical outcomes, and, so, that was certainly very exciting. That is, in the CheckMate 057 data, their biomarker, the degree of expression of PD-L1, was very closely associated with the response to Opdivo, and I’ll discuss the biomarker in a separate session. Then there was also a set of data presented with atezolizumab, which is a PD-L1 inhibitor — that, again, was randomized versus Taxotere, and, in that study, when one looks at outcomes like survival, for instance, in patients who had some degree of staining for PD-L1, there were clearly statistically significant improvements in response versus Taxotere, and it appeared that, like the CheckMate 057 data, that responses tended to be significantly more common, and clinical outcomes tend to be improved, relative to Taxotere, more specifically in patients who had a greater degree of staining for PD-L1.