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Post-Immunotherapy & Frontline Treatments for Advanced NSCLC

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: Wednesday, Dec 05, 2018



Transcript: 

Mark A. Socinski, MD: What do you do after I-O? There was some initial enthusiasm about IDO [indoleamine 2,3-dioxygenase 1] inhibitors, and we saw recent data with epacadostat. We heard there wasn’t a positive experience in melanoma with the IDO inhibitors. What seemed to be a hopeful avenues of research have turned out to be dismal. Tell us about this.

Leora Horn, MD, MSc, FRCPC: There were multiple trials ongoing with epacadostat and 5 or 6 I-O drugs that were in development, which suddenly shut down. The data in lung and melanoma and head and neck looked great at the American Society of Clinical Oncology [ASCO] 2016 Annual Meeting, but Dr. Lisa Villaruz gave us an update at the World Conference on Lung Cancer [WCLC] 2018 Annual Meeting looking at pembrolizumab [Keytruda] with or without epacadostat in the KEYNOTE and ECHO trials. That data was underwhelming. There wasn’t a better response rate to what we know of historical controls. There was a lack of advancement of progression-free survival, so I don’t think there is going to be a big role for epacadostat either in patients who are I-O naïve or I-O failed, until, perhaps, it is a biomarker issue. For right now, no one should receive it.

Mark A. Socinski, MD: There’s a lack of enthusiasm at this point, given the totality of the data. Other thoughts? We have alluded to this before. Is there anything anyone is excited about? A novel I-O combination after failure? Right now it’s PD-1 [programmed cell death protein 1] and PD-L1 [programmed death-ligand 1] inhibitors first-line. What do you do afterwards? We talked a bit about second-line. Any other thoughts?

Maximilian Hochmair, MD: We now have a trial in our clinic after chemotherapy/I-O failure. We do a re-biopsy with FoundationOne testing and then combine the PD-L1 inhibitor in combination with a targeted therapy. This seems to be very hopeful. This seems to me a good future. We have some nice results from this trial already.

Leora Horn, MD, MSc, FRCPC: The LAG-3 [lymphocyte-activation gene 3] data in melanoma looked great as well, in patients who are LAG-3 positive. We know that’s a mechanism of resistance to PD-1- and PD-L1-mutations. These drugs are being looked at in lung now as well. That’s probably the most impressive single-agent I-O drug we have, but there are probably many more coming.

Mark A. Socinski, MD: Stay tuned.

Leora Horn, MD, MSc, FRCPC: Yes.

Mark A. Socinski, MD: There is nothing that is really rising quickly as the next new standard of care after I-O. We have a lot of work to do in this population.

Transcript Edited for Clarity 

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Transcript: 

Mark A. Socinski, MD: What do you do after I-O? There was some initial enthusiasm about IDO [indoleamine 2,3-dioxygenase 1] inhibitors, and we saw recent data with epacadostat. We heard there wasn’t a positive experience in melanoma with the IDO inhibitors. What seemed to be a hopeful avenues of research have turned out to be dismal. Tell us about this.

Leora Horn, MD, MSc, FRCPC: There were multiple trials ongoing with epacadostat and 5 or 6 I-O drugs that were in development, which suddenly shut down. The data in lung and melanoma and head and neck looked great at the American Society of Clinical Oncology [ASCO] 2016 Annual Meeting, but Dr. Lisa Villaruz gave us an update at the World Conference on Lung Cancer [WCLC] 2018 Annual Meeting looking at pembrolizumab [Keytruda] with or without epacadostat in the KEYNOTE and ECHO trials. That data was underwhelming. There wasn’t a better response rate to what we know of historical controls. There was a lack of advancement of progression-free survival, so I don’t think there is going to be a big role for epacadostat either in patients who are I-O naïve or I-O failed, until, perhaps, it is a biomarker issue. For right now, no one should receive it.

Mark A. Socinski, MD: There’s a lack of enthusiasm at this point, given the totality of the data. Other thoughts? We have alluded to this before. Is there anything anyone is excited about? A novel I-O combination after failure? Right now it’s PD-1 [programmed cell death protein 1] and PD-L1 [programmed death-ligand 1] inhibitors first-line. What do you do afterwards? We talked a bit about second-line. Any other thoughts?

Maximilian Hochmair, MD: We now have a trial in our clinic after chemotherapy/I-O failure. We do a re-biopsy with FoundationOne testing and then combine the PD-L1 inhibitor in combination with a targeted therapy. This seems to be very hopeful. This seems to me a good future. We have some nice results from this trial already.

Leora Horn, MD, MSc, FRCPC: The LAG-3 [lymphocyte-activation gene 3] data in melanoma looked great as well, in patients who are LAG-3 positive. We know that’s a mechanism of resistance to PD-1- and PD-L1-mutations. These drugs are being looked at in lung now as well. That’s probably the most impressive single-agent I-O drug we have, but there are probably many more coming.

Mark A. Socinski, MD: Stay tuned.

Leora Horn, MD, MSc, FRCPC: Yes.

Mark A. Socinski, MD: There is nothing that is really rising quickly as the next new standard of care after I-O. We have a lot of work to do in this population.

Transcript Edited for Clarity 
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