Latest data from KEYNOTE 42: Pembrolizumab vs chemotherapy in treatment-naive patients (pts) with PD-L1 advanced NSCLC

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Published: 18 Apr 2019
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Prof Tony Mok - Chinese University of Hong Kong, Hong Kong

Prof Tony Mok speaks to ecancer at the European Lung Cancer Congress 2019 about the Phase 3 KEYNOTE-042 trial of pembrolizumab (MK-3475) versus platinum doublet chemotherapy in treatment-naive patients (pts) with PD-L1–positive advanced non-small cell lung cancer (NSCLC).

Prof Mok emphasises that the importance of KEYNOTE-42 is that it will support the efficacy of patients over 50% PD-L1 expression, and also to see if there is an over-survival benefit at the 1% PD-L1 expression cutoff.

He outlines the data so far, and what this means for the use of single agent pembrolizumab for the 1-49% subgroup as a first line therapy, and the small group of patients that might be applicable for this treatment as opposed to the alternative KEYNOTE-189 regimen.

Latest data from KEYNOTE 42: Pembrolizumab vs chemotherapy in treatment-naive patients (pts) with PD-L1 advanced NSCLC

Professor Tony Mok – Chinese University of Hong Kong, Hong Kong

KEYNOTE-042 is the sister trial of KEYNOTE-024 – 24, 42. So KEYNOTE-024 is actually selecting the patients of PD-L1 expression 50% or more and a primary endpoint of progression free survival. KEYNOTE-042 is a similar design however we select the patients over 1% and using overall survival as the primary endpoint. Now, the importance of KEYNOTE-042 is, number one, it will support the efficacy of the patient over 50% and, second, it’s to say how about if we use 1% as a cut-off, are we going to observe an overall survival benefit? So those are the major differences about these two studies.

In this randomised study we actually compared patients with over 1% expression, single agent pembrolizumab versus standard chemotherapy. We were actually able to demonstrate an overall survival benefit when we looked at using a cut-off at 1%, 20% or 50%. Now, the 50% subgroup of patients the advantage is actually similar with a very nice hazard ratio although the median is not as impressive as what we observed in 024. At the same time we also find that there is an improvement in the over 20% cut-off and the over 1% cut-off. But then, speaking of that, we also performed an exploratory analysis looking at the subgroup of 1-49%. With this one we did not observe any overall survival benefit. So, in other words, whether you use 1% or 20% the benefit is mostly driven by the 50% subgroup.

Now, we come to the question that can we use single agent pembrolizumab in the 1-49% subgroup as a first line? In this study we actually did not show any superiority but then there is some advantage in terms of toxicity. So I wouldn’t promote to replace chemotherapy with the single agent pembrolizumab and especially there are data from KEYNOTE-189 demonstrating that the combination of chemo with pembrolizumab is actually superior to chemotherapy. So this group probably can be considered the utilisation of a KEYNOTE-189 regimen. On the other hand, there are some patients who are physically not capable of receiving chemotherapy. This group of patients then I think we can consider the single agent use as per 042.

So that pretty well gives you a capsule of what we have learned from this important randomised study. As a matter of fact, this is has just been published by [?? 2:59] in The Lancet just about last week.