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The Future of Non-Driver Lung Adenocarcinoma

Insights From:Anders Mellemgaard, MD, Herlev University Hospital; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital;Martin Reck, MD, PhD, Hospital Grosshansdorf
Published: Thursday, Dec 22, 2016


Transcript:

Sanjay Popat, PhD
: In the non-driver non–small cell lung cancer setting, there are a number of different agents being evaluated. We’re very much in the molecular targeted era and now in the immunotherapy era. We’re starting to mix these two out, and now also mixing combinations of immunotherapy and chemotherapy. We’ve got data now that demonstrate in patients with high PD-L1 expression that immunotherapy is superior to chemotherapy. And the real question is, is immunotherapy by itself enough or should we be combining it with chemotherapy to get maximal benefit? And in the larger population of patients with low PD-L1 expression or lower PL-L1 expression, where we may not want to be using immunotherapy up front as monotherapy, what is the optimal combination? There are a number of different agents coming through. So, for example, combining the number of different PD-1 agents with CTLA4 inhibitors is also looking very interesting to try and drive up the PD-L1 expression.

Anders Mellemgaard, MD: Any question about the future is difficult to answer, and had you asked me that question 3 years ago, I probably wouldn’t have said that immune therapy is as important as we think about it right now. So, this is going to be difficult. Personally, I think that we can use the drugs that we have better if we have better predictors. If we can get tests that will make it more possible for us to select patients for the right treatment, that would be a tremendous help, even with the treatments that we have today.

Another thing that I think we’ll see in the future is sequence and combinations. We’ll get more information about how to use the drugs right, how to combine, and I’m pretty sure we’ll also see some disappointments there. Because whenever we test combinations, we sometimes see toxicity that we didn’t anticipate. So, we’ll still rely on clinical trials and testing and development, and it is not going to go very fast ahead. But I do see a future where we have many more treatments than we have today. And I do think the immunotherapies are actually providing us with a whole new area of development. I think it’s interesting that we’re moving from a situation where we treat the cancer cell with chemotherapy to a situation where we’re treating the cancer in a microenvironment with the anti-antigenic agents, with the immune therapies, etc. I think we’re getting better at understanding the complexity of the cancer process. What we’re still not good at is really appreciating the enormous heterogeneity and the dynamics of the cancer process. And for that reason, I think we still have to be humble and we still have to say that the future will bring advances, but also disappointments.

Martin Reck, MD, PhD: Management of patients with lung cancer is changing. We have seen substantial improvements in second-line therapies. We have new treatment principles, like the immunotherapy. We have a reactivation of old principles, like antiangiogenesis. And from a conceptual way of thinking, it would be great to see the combination of these different strategies. So, combinations will be the key point of investigation in the upcoming year. We will see multiple combination trials combining immunotherapy with different treatment approaches. In particular, the combination of antiangiogenic approaches, like nintedanib with immune modulators, would be of high clinical interest because they really might increase the efficacy of anti-immune therapies.

Transcript Edited for Clarity
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Transcript:

Sanjay Popat, PhD
: In the non-driver non–small cell lung cancer setting, there are a number of different agents being evaluated. We’re very much in the molecular targeted era and now in the immunotherapy era. We’re starting to mix these two out, and now also mixing combinations of immunotherapy and chemotherapy. We’ve got data now that demonstrate in patients with high PD-L1 expression that immunotherapy is superior to chemotherapy. And the real question is, is immunotherapy by itself enough or should we be combining it with chemotherapy to get maximal benefit? And in the larger population of patients with low PD-L1 expression or lower PL-L1 expression, where we may not want to be using immunotherapy up front as monotherapy, what is the optimal combination? There are a number of different agents coming through. So, for example, combining the number of different PD-1 agents with CTLA4 inhibitors is also looking very interesting to try and drive up the PD-L1 expression.

Anders Mellemgaard, MD: Any question about the future is difficult to answer, and had you asked me that question 3 years ago, I probably wouldn’t have said that immune therapy is as important as we think about it right now. So, this is going to be difficult. Personally, I think that we can use the drugs that we have better if we have better predictors. If we can get tests that will make it more possible for us to select patients for the right treatment, that would be a tremendous help, even with the treatments that we have today.

Another thing that I think we’ll see in the future is sequence and combinations. We’ll get more information about how to use the drugs right, how to combine, and I’m pretty sure we’ll also see some disappointments there. Because whenever we test combinations, we sometimes see toxicity that we didn’t anticipate. So, we’ll still rely on clinical trials and testing and development, and it is not going to go very fast ahead. But I do see a future where we have many more treatments than we have today. And I do think the immunotherapies are actually providing us with a whole new area of development. I think it’s interesting that we’re moving from a situation where we treat the cancer cell with chemotherapy to a situation where we’re treating the cancer in a microenvironment with the anti-antigenic agents, with the immune therapies, etc. I think we’re getting better at understanding the complexity of the cancer process. What we’re still not good at is really appreciating the enormous heterogeneity and the dynamics of the cancer process. And for that reason, I think we still have to be humble and we still have to say that the future will bring advances, but also disappointments.

Martin Reck, MD, PhD: Management of patients with lung cancer is changing. We have seen substantial improvements in second-line therapies. We have new treatment principles, like the immunotherapy. We have a reactivation of old principles, like antiangiogenesis. And from a conceptual way of thinking, it would be great to see the combination of these different strategies. So, combinations will be the key point of investigation in the upcoming year. We will see multiple combination trials combining immunotherapy with different treatment approaches. In particular, the combination of antiangiogenic approaches, like nintedanib with immune modulators, would be of high clinical interest because they really might increase the efficacy of anti-immune therapies.

Transcript Edited for Clarity
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