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Combining and Sequencing Immunotherapies in NSCLC

Panelists:Benjamin Levy, MD, Mount Sinai Health Systems, ; John W. Longshore, PhD, Carolinas Pathology Group; Gregory J. Riely, MD, PhD, Weill Cornell Medical College; Mark A. Socinski, MD, University of Pittsburgh; Thomas E. Stinchcombe, MD, University of North Carolina at Chapel Hill; Jared Weiss, MD, University of North Carolina School of Medicine
Published: Monday, Jun 20, 2016


Transcript:

Mark A. Socinski, MD:
One of the issues is kind of thinking forward with the advent of immunotherapy. We have PD-1 agents now. We’re likely to have PD-L1 drugs. Do those drugs work after PD-1? How do we choose? What patient does better on one or the other? And then you add the CTLA4 on top of it? And then you add a lot of other targets that are coming down the road, all those other targets that are there, antibodies are coming out. The question is how much can we muck with the immune system, and get away with it to our benefit is one issue of toxicity? I worry about that. But, where do you all see immunotherapy five years from now? Are we going to go beyond the PD-L1 agents? What are people’s thoughts?

Gregory J. Riely, MD, PhD: I think we’re going to go beyond PD-L1, and we’re going to go beyond CTLA4, that’s clear. But, I think probably the near-term thing is moving into first-line. So, up until now, this has all been second-line trials, and I think we’ve seen enough response rate and progression-free survival advantage in the second-line setting to move these into first-line. There are lots of ongoing first-line studies comparing chemotherapy to single agent immunotherapy or combined immunotherapy. And this data, as it reads out, is really going to be exciting because it’s going to transform how we think about first-line, if any of them are positive.

Mark A. Socinski, MD: Let me ask you this. Patients know about immunotherapies. They come in asking for immunotherapies.

Jared Weiss, MD: Sure, there are advertisements on TV.

Mark A. Socinski, MD: Any patient you would treat with immunotherapy first-line at this point?

Benjamin P. Levy, MD: I would say if you look at the data with single-agent checkpoint inhibitor in an unenriched patient population, the response rate is around 23%, 25%, which is very similar to chemotherapy.

Mark A. Socinski, MD: Less toxic, a lot more expensive.

Benjamin P. Levy, MD: A lot less toxic. We’re going to give chemotherapy, eventually. So, I think off of a clinical trial. And we’ve seen a lot of patients getting second opinions who are wanting immunotherapy as their initial treatment. And I can understand the enthusiasm based on all the TV commercials and all the awareness. I would not treat a patient with single-agent checkpoint inhibitor, treatment-naive patient.

Jared Weiss, MD: So, I would say outside the context of a clinical trial, I have not done it yet. I will say there are a few contexts where I might be at least tempted. We have data now, for both elderly patients and PS2 patients, that doublets are better than single agents. And, that actually even held up for the PS2 elderly. But, when I have a patient who I’m really hesitant, for whatever reason—and there are a variety of obvious reasons that I’m really hesitant about whether they’re candidate for doublet therapy—these agents are much, much better-tolerated. And that is a game changer. I think that at least needs to be explored in a trial, those poorer performance status patients.

Mark A. Socinski, MD: Well, gentlemen, this discussion has been great. I want to thank all of you for participating in this. We discussed a lot of information on the treatment of non-small cell carcinoma lung in the adenocarcinoma population. Before we end this discussion, I’d like to get some final thoughts from each of the panelists. I’ll start to my right with Dr. Riely.

Gregory J. Riely, MD, PhD: So, I think the biggest thing I’m excited about in the last few years in treatment of lung cancer is this notion that we now have first and second-line targeted therapy for both ALK-positive and EGFR-mutant disease. This really separates out these targeted patient populations to get targeted therapies as both first and second-line. And I think this is a natural extension of where we started 10 years ago in this field.

Mark A. Socinski, MD: Ben.

Benjamin P. Levy, MD: I’ll make a pitch for plasma genotyping. I know it’s very early on, but with all the issues and barriers with tissue interrogation, I think that there will be eventual routine clinic use of a reliable predictive molecular proxy of tumor biology that you can get from a non-invasive plasma test.

Mark A. Socinski, MD: Tom.

Thomas E. Stinchcombe, MD: I agree with what Ben and Greg said, but I think I’m really looking forward to the movement of immunotherapies to the frontline, potentially after the chemoradiotherapy segment because most of our patients don’t have an actionable mutation, and we’d like to see something change the paradigm in those two settings.

Mark A. Socinski, MD: It’s always tough to be last but...

Jared Weiss, MD: I’ve been dazzled by the acceleration of progress that we’ve had in our clinical trials, and how much more promising our clinical trials are than they were even just 5 years ago. And, so, I’ll make a pitch that we should lower our threshold to put patients on clinical trials, including even in first-line for the most promising of these agents.

Mark A. Socinski, MD: Thank you, gentlemen. On behalf of our panel, we thank you for joining us, and we hope you found this OncLive Peer Exchange informative.

Transcript Edited for Clarity
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Transcript:

Mark A. Socinski, MD:
One of the issues is kind of thinking forward with the advent of immunotherapy. We have PD-1 agents now. We’re likely to have PD-L1 drugs. Do those drugs work after PD-1? How do we choose? What patient does better on one or the other? And then you add the CTLA4 on top of it? And then you add a lot of other targets that are coming down the road, all those other targets that are there, antibodies are coming out. The question is how much can we muck with the immune system, and get away with it to our benefit is one issue of toxicity? I worry about that. But, where do you all see immunotherapy five years from now? Are we going to go beyond the PD-L1 agents? What are people’s thoughts?

Gregory J. Riely, MD, PhD: I think we’re going to go beyond PD-L1, and we’re going to go beyond CTLA4, that’s clear. But, I think probably the near-term thing is moving into first-line. So, up until now, this has all been second-line trials, and I think we’ve seen enough response rate and progression-free survival advantage in the second-line setting to move these into first-line. There are lots of ongoing first-line studies comparing chemotherapy to single agent immunotherapy or combined immunotherapy. And this data, as it reads out, is really going to be exciting because it’s going to transform how we think about first-line, if any of them are positive.

Mark A. Socinski, MD: Let me ask you this. Patients know about immunotherapies. They come in asking for immunotherapies.

Jared Weiss, MD: Sure, there are advertisements on TV.

Mark A. Socinski, MD: Any patient you would treat with immunotherapy first-line at this point?

Benjamin P. Levy, MD: I would say if you look at the data with single-agent checkpoint inhibitor in an unenriched patient population, the response rate is around 23%, 25%, which is very similar to chemotherapy.

Mark A. Socinski, MD: Less toxic, a lot more expensive.

Benjamin P. Levy, MD: A lot less toxic. We’re going to give chemotherapy, eventually. So, I think off of a clinical trial. And we’ve seen a lot of patients getting second opinions who are wanting immunotherapy as their initial treatment. And I can understand the enthusiasm based on all the TV commercials and all the awareness. I would not treat a patient with single-agent checkpoint inhibitor, treatment-naive patient.

Jared Weiss, MD: So, I would say outside the context of a clinical trial, I have not done it yet. I will say there are a few contexts where I might be at least tempted. We have data now, for both elderly patients and PS2 patients, that doublets are better than single agents. And, that actually even held up for the PS2 elderly. But, when I have a patient who I’m really hesitant, for whatever reason—and there are a variety of obvious reasons that I’m really hesitant about whether they’re candidate for doublet therapy—these agents are much, much better-tolerated. And that is a game changer. I think that at least needs to be explored in a trial, those poorer performance status patients.

Mark A. Socinski, MD: Well, gentlemen, this discussion has been great. I want to thank all of you for participating in this. We discussed a lot of information on the treatment of non-small cell carcinoma lung in the adenocarcinoma population. Before we end this discussion, I’d like to get some final thoughts from each of the panelists. I’ll start to my right with Dr. Riely.

Gregory J. Riely, MD, PhD: So, I think the biggest thing I’m excited about in the last few years in treatment of lung cancer is this notion that we now have first and second-line targeted therapy for both ALK-positive and EGFR-mutant disease. This really separates out these targeted patient populations to get targeted therapies as both first and second-line. And I think this is a natural extension of where we started 10 years ago in this field.

Mark A. Socinski, MD: Ben.

Benjamin P. Levy, MD: I’ll make a pitch for plasma genotyping. I know it’s very early on, but with all the issues and barriers with tissue interrogation, I think that there will be eventual routine clinic use of a reliable predictive molecular proxy of tumor biology that you can get from a non-invasive plasma test.

Mark A. Socinski, MD: Tom.

Thomas E. Stinchcombe, MD: I agree with what Ben and Greg said, but I think I’m really looking forward to the movement of immunotherapies to the frontline, potentially after the chemoradiotherapy segment because most of our patients don’t have an actionable mutation, and we’d like to see something change the paradigm in those two settings.

Mark A. Socinski, MD: It’s always tough to be last but...

Jared Weiss, MD: I’ve been dazzled by the acceleration of progress that we’ve had in our clinical trials, and how much more promising our clinical trials are than they were even just 5 years ago. And, so, I’ll make a pitch that we should lower our threshold to put patients on clinical trials, including even in first-line for the most promising of these agents.

Mark A. Socinski, MD: Thank you, gentlemen. On behalf of our panel, we thank you for joining us, and we hope you found this OncLive Peer Exchange informative.

Transcript Edited for Clarity
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TitleExpiration DateCME Credits
Community Practice Connections™: 18th Annual International Lung Cancer Congress®Oct 31, 20181.5
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