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Anti-PD-1 Therapy in Metastatic Melanoma

Panelists: Axel Hauschild, MD, University Hospital Schleswig-Holstein; Michael A. Davies, MD, PhD UT MD Anderson Cancer Center; Jason J. Luke, MD, FACP, University of Chicago; Caroline Robert, MD, PhD Gustave-Roussy; Merrick I. Ross, MD UT MD Anderson Cancer Center
Published: Friday, Dec 21, 2018

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Transcript: 

Axel Hauschild, MD:
When we discuss stage IV melanoma now, I think it’s good to provide a quick overview on ASCO [American Society of Clinical Oncology] 2018. Most of the trials that have been released as an update at ASCO with long-term survival data were done on PD-1 [programmed cell death protein 1] antibodies. Can you summarize KEYNOTE-001 and KEYNOTE-006, Caroline, and the latest findings from ASCO in terms of long-term survival? For the first time, we have seen 5-year survival data not only on nivolumab, which was presented 2 years before with a 34% 5-year survival and was exciting. Now we have the data on pembrolizumab from KEYNOTE-001 and KEYNOTE-006.

Caroline Robert, MD, PhD: KEYNOTE-001 is a huge phase I trial with 655 patients. It’s quite a heterogeneous population because we had patients who were pretreated and about 100 patients were naive. The results are a little bit better for the naive patients, but, still, we have this…

I’m not totally 100% sure that we have the plateau that we have with ipilimumab, honestly. I think we still all hope to see this very flat plateau, even though we should begin to see it with anti–PD-1 single-agent therapy. If it’s like ipilimumab, and it begins at 3 years, we should have some flattening of the curve.

But we have the KEYNOTE-006 trial that is more homogenous. In this trial, we also have some patients who are being looked at in the second-line setting. Some of the BRAF-mutant patients had rapid progression of their disease. So here we also have results. We have long-term results. We have totally consumed the benefit, in terms of overall survival in the KEYNOTE-006 trial. The phase I trial was a single-arm study. We also have this new overall survival that is more than 30 months. Interestingly, the very recent targeted therapy overall survival with binimetinib and encorafenib was also 33 months. So when we look only at the median, it is not different. I think that we will probably see a more flattening curve with anti–PD-1 therapy. We also have the update to another trial, which is very important. Maybe we will talk about that later?

Axel Hauschild, MD: Yes, we’ll talk about that later.

Caroline Robert, MD, PhD: We are interested to know whether we have to add anti-CTLA-4 even at the price of a higher toxicity. But right now, I think anti–PD-1 agents really have met their objective. We have very good overall survival and no bad surprises in terms of tolerance. Long-term tolerance data are going to be published soon. We have very long-term adverse events with the collection of the data from all the KEYNOTE trials. So I think we are quite comfortable, and these drugs are widely used.

Axel Hauschild, MD: It’s very consistent data. They reported a 34% 5-year survival for pembrolizumab in first-line and second-line patients, so it’s a mixed population. But in the 150 patients who just received first-line treatment, it’s something like 40% to 42%. It’s a little more than 40%, which is really nice because we have an idea of what we can consider from others. So this is the threshold for upcoming clinical trial results.


Transcript Edited for Clarity
 

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<iframe width="560" height="315" src="https://www.youtube.com/embed/MgcfKOFNOis?rel=0&amp;autoplay=1&amp;fs=0" frameborder="0" allow="accelerometer; autoplay; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe>

Transcript: 

Axel Hauschild, MD:
When we discuss stage IV melanoma now, I think it’s good to provide a quick overview on ASCO [American Society of Clinical Oncology] 2018. Most of the trials that have been released as an update at ASCO with long-term survival data were done on PD-1 [programmed cell death protein 1] antibodies. Can you summarize KEYNOTE-001 and KEYNOTE-006, Caroline, and the latest findings from ASCO in terms of long-term survival? For the first time, we have seen 5-year survival data not only on nivolumab, which was presented 2 years before with a 34% 5-year survival and was exciting. Now we have the data on pembrolizumab from KEYNOTE-001 and KEYNOTE-006.

Caroline Robert, MD, PhD: KEYNOTE-001 is a huge phase I trial with 655 patients. It’s quite a heterogeneous population because we had patients who were pretreated and about 100 patients were naive. The results are a little bit better for the naive patients, but, still, we have this…

I’m not totally 100% sure that we have the plateau that we have with ipilimumab, honestly. I think we still all hope to see this very flat plateau, even though we should begin to see it with anti–PD-1 single-agent therapy. If it’s like ipilimumab, and it begins at 3 years, we should have some flattening of the curve.

But we have the KEYNOTE-006 trial that is more homogenous. In this trial, we also have some patients who are being looked at in the second-line setting. Some of the BRAF-mutant patients had rapid progression of their disease. So here we also have results. We have long-term results. We have totally consumed the benefit, in terms of overall survival in the KEYNOTE-006 trial. The phase I trial was a single-arm study. We also have this new overall survival that is more than 30 months. Interestingly, the very recent targeted therapy overall survival with binimetinib and encorafenib was also 33 months. So when we look only at the median, it is not different. I think that we will probably see a more flattening curve with anti–PD-1 therapy. We also have the update to another trial, which is very important. Maybe we will talk about that later?

Axel Hauschild, MD: Yes, we’ll talk about that later.

Caroline Robert, MD, PhD: We are interested to know whether we have to add anti-CTLA-4 even at the price of a higher toxicity. But right now, I think anti–PD-1 agents really have met their objective. We have very good overall survival and no bad surprises in terms of tolerance. Long-term tolerance data are going to be published soon. We have very long-term adverse events with the collection of the data from all the KEYNOTE trials. So I think we are quite comfortable, and these drugs are widely used.

Axel Hauschild, MD: It’s very consistent data. They reported a 34% 5-year survival for pembrolizumab in first-line and second-line patients, so it’s a mixed population. But in the 150 patients who just received first-line treatment, it’s something like 40% to 42%. It’s a little more than 40%, which is really nice because we have an idea of what we can consider from others. So this is the threshold for upcoming clinical trial results.


Transcript Edited for Clarity
 
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