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The Current State of Advanced NSCLC Treatment & Contingencies

Panelists: Mark A. Socinski, MD, Florida Hospital Cancer Institute; Maximilian Hochmair, MD, Otto Wagner Spital; Suresh Senan, MRCP, FRCR, PhD, VU University Medical Center; Leora Horn, MD, MSc, FRCPC, Vanderbilt University Medical Center; Thomas E. Stinchcombe, MD, Duke University Health System
Published: Thursday, Jan 03, 2019



Transcript:

Mark A. Socinski, MD:
This has been extremely informative. Before we end this discussion, I’d like to get some closing thoughts from each of our patients. I’ll start with Maximillian.

Maximilian Hochmair, MD: I learned a lot on my own. It’s important to have key relationships with the pathologists to get biomarkers to decide which drug is the best. We have immunotherapy [I-O] combinations with chemotherapy for all non–small cell lung cancer patients who are nondriven. Even the patients who are biomarker driven will receive, in later lines, a combination I-O with chemotherapy. When we compare our landscape with 10 years ago, it’s much more complicated. We have many subgroups, such as ALK and EGFR, all of which can use different drugs. It’s exciting for patients and us.

Thomas E. Stinchcombe, MD: Maximillian hit on a critical thing with integrating the pathology and biomarker selections, because that’s really critical to do up-front. I’m excited for the potential with liquid biopsies. They’re not going to necessarily replace tumor biopsies, but they may help us with patients who have insufficient tissue or other problems. I-O continues to dominate the paradigm for most patients. I’m eager to see the CheckMate 227 data in their totality because I think the next big question is, is there going to be a double I-O combination? Or is chemotherapy the best platform to combine with I-O? Some work on the mechanisms of resistance for the people who progress on I-O because it’s a heterogeneous patient population. I don’t think clinical factors are going to be sufficient to guide us.

Mark A. Socinski, MD: Leora?

Leora Horn, MD, MSc, FRCPC: It’s hard to follow that.

Mark A. Socinski, MD: I’m sure you can come up with something.

Leora Horn, MD, MSc, FRCPC: It’s never been a more exciting time. There are a lot of data coming out showing various options for therapy. In the United States, there are a lot of patients who don’t get treated. How do we get that message out there that there are well-tolerated options? Expanding on what Thomas said, it is important to understand not only the mechanisms of resistance to I-O but who should get these drugs to begin with and how we should administer them. Who should receive more than just checkpoint inhibitors? For targeted therapies, how do we make the responses as high as with checkpoint inhibitors? We’ve still got a lot to learn.

Mark A. Socinski, MD: Suresh?

Suresh Senan, MRCP, FRCR, PhD: To me, the big excitement is the potential for improving the cure in stage III. The big challenge is, how do we beat the PACIFIC regimen? The design of clever trials and broader identification of biomarkers to differentiate the subgroups. Stage III is heterogeneous, and we need to tailor the approach, so let’s work toward that. Stage IV for me is a big challenge to design trials with locally ablated therapy—low-volume oligometastatic treatment. Yesterday, the presidential subset prostate cancer in the STAMPEDE trial, showed a survival benefit from low-volume disease with an addition of radiotherapy. You have to keep in mind that the majority of patients either don’t respond to I-O or fail at some point. It could lead to a standard approach with or without radiation. That abscopal effect is, to me, not a reality yet. It’s more like tailoring and sequencing the right modalities. Stereotactic radiotherapy, for example, is locally ablative up-front for 1 arm, and medicated on the other. It would be useful to see how we could help these patients. We need big trials.

Mark A. Socinski, MD: You hit the nail on the head when you said it’s an exciting time. I started in lung cancer when, as a fellow, we would argue about whether or not lung cancer could be treated at all. There were trials of platinum-based therapy versus the best supportive care. When you think about it, it has only been 25 years since we endorsed treatment as changing the natural history of the disease, and to see where we’ve come today, with a plethora of molecular subtype studies with targeted therapies—it’s amazing. Then, with what is known as the “immuno tsunami,” we now have a large population of patients eligible to receive I-O. The argument is, who receives monotherapy or combination therapy? If you get combination therapy, what’s the best chemotherapy platform? It is a really exciting time. It comes down to us having the ability to help our patients more. People are living longer and with a better quality of life since we’ve made these changes in therapeutic options.

So thank you all for your contributions to this discussion. On behalf of our panel, we thank you for joining us, and we hope you found this peer-exchange discussion to be useful and informative. Thank you for joining us.

Transcript Edited for Clarity.

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Transcript:

Mark A. Socinski, MD:
This has been extremely informative. Before we end this discussion, I’d like to get some closing thoughts from each of our patients. I’ll start with Maximillian.

Maximilian Hochmair, MD: I learned a lot on my own. It’s important to have key relationships with the pathologists to get biomarkers to decide which drug is the best. We have immunotherapy [I-O] combinations with chemotherapy for all non–small cell lung cancer patients who are nondriven. Even the patients who are biomarker driven will receive, in later lines, a combination I-O with chemotherapy. When we compare our landscape with 10 years ago, it’s much more complicated. We have many subgroups, such as ALK and EGFR, all of which can use different drugs. It’s exciting for patients and us.

Thomas E. Stinchcombe, MD: Maximillian hit on a critical thing with integrating the pathology and biomarker selections, because that’s really critical to do up-front. I’m excited for the potential with liquid biopsies. They’re not going to necessarily replace tumor biopsies, but they may help us with patients who have insufficient tissue or other problems. I-O continues to dominate the paradigm for most patients. I’m eager to see the CheckMate 227 data in their totality because I think the next big question is, is there going to be a double I-O combination? Or is chemotherapy the best platform to combine with I-O? Some work on the mechanisms of resistance for the people who progress on I-O because it’s a heterogeneous patient population. I don’t think clinical factors are going to be sufficient to guide us.

Mark A. Socinski, MD: Leora?

Leora Horn, MD, MSc, FRCPC: It’s hard to follow that.

Mark A. Socinski, MD: I’m sure you can come up with something.

Leora Horn, MD, MSc, FRCPC: It’s never been a more exciting time. There are a lot of data coming out showing various options for therapy. In the United States, there are a lot of patients who don’t get treated. How do we get that message out there that there are well-tolerated options? Expanding on what Thomas said, it is important to understand not only the mechanisms of resistance to I-O but who should get these drugs to begin with and how we should administer them. Who should receive more than just checkpoint inhibitors? For targeted therapies, how do we make the responses as high as with checkpoint inhibitors? We’ve still got a lot to learn.

Mark A. Socinski, MD: Suresh?

Suresh Senan, MRCP, FRCR, PhD: To me, the big excitement is the potential for improving the cure in stage III. The big challenge is, how do we beat the PACIFIC regimen? The design of clever trials and broader identification of biomarkers to differentiate the subgroups. Stage III is heterogeneous, and we need to tailor the approach, so let’s work toward that. Stage IV for me is a big challenge to design trials with locally ablated therapy—low-volume oligometastatic treatment. Yesterday, the presidential subset prostate cancer in the STAMPEDE trial, showed a survival benefit from low-volume disease with an addition of radiotherapy. You have to keep in mind that the majority of patients either don’t respond to I-O or fail at some point. It could lead to a standard approach with or without radiation. That abscopal effect is, to me, not a reality yet. It’s more like tailoring and sequencing the right modalities. Stereotactic radiotherapy, for example, is locally ablative up-front for 1 arm, and medicated on the other. It would be useful to see how we could help these patients. We need big trials.

Mark A. Socinski, MD: You hit the nail on the head when you said it’s an exciting time. I started in lung cancer when, as a fellow, we would argue about whether or not lung cancer could be treated at all. There were trials of platinum-based therapy versus the best supportive care. When you think about it, it has only been 25 years since we endorsed treatment as changing the natural history of the disease, and to see where we’ve come today, with a plethora of molecular subtype studies with targeted therapies—it’s amazing. Then, with what is known as the “immuno tsunami,” we now have a large population of patients eligible to receive I-O. The argument is, who receives monotherapy or combination therapy? If you get combination therapy, what’s the best chemotherapy platform? It is a really exciting time. It comes down to us having the ability to help our patients more. People are living longer and with a better quality of life since we’ve made these changes in therapeutic options.

So thank you all for your contributions to this discussion. On behalf of our panel, we thank you for joining us, and we hope you found this peer-exchange discussion to be useful and informative. Thank you for joining us.

Transcript Edited for Clarity.
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