Medicine Matters oncology

So here at ESMO 2019, we've had data presented from the CheckMate 227 study. This is a long going and now presented-- fully presented-- trial for patients in the frontline advanced non-small cell lung cancer setting. Here, a large number of patients were randomized depending on their PD-L1 status. For patients that were PD-L1 positive, they were randomized to either nivo/ipi, nivo, or chemotherapy. In the primary outcome of that study, the investigators demonstrated that nivo/ipi was superior to chemotherapy, but nivo itself was not superior to chemotherapy.

However, the important thing is to look at which of the groups of patients that benefit from nivo/ipi, because at the moment, the comparators that we have in clinical practice are pembrolizumab monotherapy or pembro chemo. When the investigators did PD-L1 analysis, they demonstrated that the benefit was very much driven by the more than 50% PD-L1 positive group. So this is the group that really benefits the greatest from nivo/ipi.

So as a clinician, one, therefore, can have the choice to use nivo/ipi, which does have a slightly greater adverse event profile rather than single agent immune checkpoint inhibitor therapy, for a relatively similar benefit when it comes to the hazard ratio for overall survival compared to chemotherapy.

In the second group of patients, these are the PD-L1 negative group of patients, they were randomized to either nivo/ipi, chemo alone, or chemo with nivo. When we look at the outcomes there, again we see the greatest benefit with nivo/ipi over chemotherapy. However, this wasn't a pre-specified primary or secondary endpoint. This was an exploratory, predefined endpoint. And of course, this, therefore, does represent a potential treatment choice for patients in this setting, bearing in mind that the comparator in this scenario, in real life is currently pembro chemo. And so therefore, the adverse event profile of each of these two different regimes needs to be borne in mind.