Medicine Matters oncology

And I've presented the KEYNOTE-024 five year update. And if you remember, the KEYNOTE-024 was a first line treatment trial for patients with advanced non-small cell lung cancer with the PDL1 tumor proportion score of greater than or equal to 50%, but could not have ALG or EGFR alterations. These patients were randomized to pembrolizumab or chemotherapy. Pembrolizumab was continued for up to two years, and those patients who were treated with chemotherapy were allowed to cross over at the time of progression of disease.

So I've presented the five year overall survival update, and quite excitingly, we were able to show that patients treated with pembrolizumab as a single agent had a five year overall survival rate of 32%. Patients who were treated with chemotherapy at a five year overall survival rate of 16%. This was despite a 66% crossover rate for those patients treated with chemotherapy who crossed over to receive pembrolizumab.

But I think this was one of the first studies-- phase III studies-- that have demonstrated a five year overall survival advantage when being treated with single-agent pembrolizumab. Again, this was a group of patients who had high PDL1 or a tumor proportion score 50% or greater. I'm happy to see the five year overall survival rate improve, and I'm hoping that we can say, now, that we can cure some of our patients with metastatic disease, but we have a long ways to go for the majority of the patients.

Right now, the higher the PDL1, the more likely the response. So again, for this particular trial, and here in the US, we're more likely to give single-agent pembrolizumab for those patients with high PDL1, a tumor proportion score of 50% or greater. So that's been pretty consistent, at least for non-small cell lung cancer. Now, if you have any PDL1 or just a PDL1 positive tumor, 1% or greater, pembrolizumab, as well as atezolizumab are also approved for use in the first line setting.

But I would say most of us feel like, for those patients who present to us with first-- and who have never been treated with advanced disease, if their PDL1 score is greater than 50%, then we're more likely to give single-agent pembrolizumab. Now, folks have also looked at tumor mutation burden, and the way I explain it, the higher the number of mutations that your cancer has, the more likely your immune system can recognize an abnormal protein that those mutations make.

But that has not been consistent throughout the different studies, and so the cutoffs that are used-- we're still working on trying to figure out how best to use that type of biomarker. I think the biomarkers definitely do-- and the performance-- do change when you add chemotherapy to immunotherapy, where the biomarkers may not matter as much when we're adding chemotherapy to immunotherapy.

Well, I think the unanswered question, at least the most immediate, is what does chemotherapy do to pembrolizumab five year overall survival, and so I'm very excited to hear about the next steps, or the next results in KEYNOTE-189 and the other KEYNOTE studies that combine pembrolizumab map with chemotherapy. I hope to hear about improved five year overall survival, but I think we just need to see the data.

And I think trying to figure out how to make oncology more precise for patients, like you just asked me about for biomarkers, trying to figure out a better way of deciding who should receive immunotherapy by itself, who should receive immunotherapy plus chemotherapy, or who should receive combination immunotherapy. And we just don't have the tools yet to figure that out, but a lot of trials are ongoing to look at that.