Using the Morbidity and Mortality Conference Model to Explore and Improve Community-Based Oncology Care (Video Program)KEYNOTE-024 trial evaluating pembrolizumab versus platinum-based chemotherapy as first-line therapy for advanced NSCLC with a PD-L1 tumor proportion score of 50% or greater
2:52 minutes.
TRANSCRIPTION:
DR WAKELEE: It was a randomized Phase III trial for patients who had — using the assay with the 22C3 antibody. And it’s important to mention there are multiple different PD-L1 antibodies that are being used in conjunction with the different checkpoint inhibitors. DR LOVE: But they’re all IHC tests? DR WAKELEE: They’re all IHC tests. And there’s variability, though. There’s been some analyses done showing that, for most of them, there’s actually fairly good concordance. But still, this was specifically with that clone, the 22C3 clone, looking for patients who had at least a 50% expression cut point. So it’s a pretty high cut point. And it ended up being about 30% of patients or so who would qualify. And so in that trial then, patients who were eligible, who met that cut point — and I think they screened close to 2,000 patients to get the patients who went on the trial — they were randomized to either get pembrolizumab or to get platinum-doublet chemotherapy. And what the study showed was a clear progression-free survival benefit of a few months and then also an overall survival benefit, which was what was presented. Now the overall survival benefit was based on percentage alive, I think, at 6 months. And so we don’t know what does that mean long, long term, but the hazard ratio was quite good. It was about 0.6. DR LOVE: Also the response rate was higher. DR WAKELEE: Yes, and the response rate was higher also. And so we had response, progression-free and overall survival. Now again, it wasn’t a median overall survival. It was at a 6-month time point. And both numbers were quite good, but it was still statistically significantly better. And so I think that does change practice, such that we are, I think, now obligated in any patient with a non-small cell lung cancer to test for PD-L1 and, if they’re positive, to think about offering them that. Now, the caveat, of course, is those drugs are not — pembrolizumab is not without toxicity. And I think where I’m most cautious is in patients who have any sort of underlying autoimmune disease. So that’s why I’m a little hesitant. I know that there’s some variation in practice, but from my standpoint, we’re now making sure those patients are getting their PD-L1 testing results back as quickly as we’re getting EGFR and ALK and ROS. And that’s going to help guide. There’s going to be the PD-L1-high expressers, the mutation-positive patients. And they’re probably not going to be overlapping for the most part. And then everybody else. DR LOVE: What do we know about time to response, checkpoint inhibitor versus chemo? DR WAKELEE: It’s probably not that different. I mean, there was this rumor that it would take longer before they would respond. I’ve definitely had patients who responded very quickly to checkpoint inhibitors, just as we’ve all had chemo patients where you know within a few days that they’re responding to the chemo just because they feel better. Or, if they’re having tumor fevers, those go away. So I wouldn’t exclude someone based on being too sick from getting a checkpoint inhibitor. |