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Advancing the Treatment of Nondriver Metastatic NSCLC

Insights From: Hossein Borghaei, DO, Fox Chase Cancer Center; Corey J. Langer, MD, Perelman School of Medicine; Vassiliki Papadimitrakopoulou, MD, MD Anderson Cancer Center
Published: Monday, Aug 27, 2018



Transcript: 

Vassiliki Papadimitrakopoulou, MD: I am very excited about the opportunities for research in patients who are immunotherapy-exposed. We’re seeing early signals with novel agents trying to transform tumors that are called “too hot” and trying to transform patients’ tumors that are unresponsive to immunotherapy to tumors that are responsive. I’m also very excited about the fact that we’re seeing long progression-free survival, duration of responses, and overall survival for investigational arms in all immunotherapy trials. The hope is that some of these patients will receive long-term benefit, and maybe we can use the term cure for our patients with metastatic disease in the future.

Hossein Borghaei, DO: What I’m really excited about is all the new opportunities we have. Clearly, I’m excited about the I-O/chemotherapy combinations because to me, surprisingly, they’re working really well in terms of clinical efficacy and toxicity. I like that, and I think I can use that in my clinic, and I am using it. I would like to see more immuno-oncology combinations. I want to see if we can push chemotherapy further and further down the line and not have to use it in the up-front setting. I realize we might be years away from a scenario in which everybody gets a very active, well-tolerated I-O/I-O combination. But I think we are beginning to see a partition, so if you have somebody with high tumor mutational burden and low PD-L1 expression, you might want to have the option of I-O/I-O therapy, as opposed to just chemotherapy, and at least discuss that with the patient. If you have a patient who, for whatever reason, is unwilling to get chemotherapy or cannot get chemotherapy, having an I-O/I-O combination is a very legitimate and reasonable option.

I think what we haven’t answered is this question of sequencing. Should everybody get everything up front, or should we still use sequential therapy? Now, whether that’s I-O followed by chemotherapy or chemotherapy followed by I-O, I think this sort of question needs to be answered. If survival is going to be the same, and we can start with an I-O single agent that’s less toxic and as efficacious, then at the time of progression use chemotherapy, and the overall survival is going to be basically the same, why not start with something that’s a little less complicated, a little less toxic, and then sequence the treatment?

I think some of these questions will be answered in the ensuing years, but for now, we’re going to be overwhelmed with a wealth of immuno-oncology combinations that are going to be coming at us in various meetings. Our challenge is to figure out which one is more efficacious, which one is well tolerated, and which one can challenge this I-O plus chemotherapy in the frontline setting.

Corey J. Langer, MD: Immunotherapy has, without question, absolutely transformed our practice. I have to confess, I was an immunotherapy skeptic who was informed on prior experience with other agents that were highly toxic and not particularly efficacious. But the emergence of first nivolumab, then pembrolizumab, then atezolizumab—all strikingly positive in phase III studies in the second-line setting, and now in repeatedly positive trials in the frontline setting, either alone or in combination with chemotherapy—has absolutely altered how we practice medical oncology in the thoracic clinic, and only for the better. The patients are the ultimate beneficiaries. As time goes on, our learning curve improves, and we’re better able to manage the toxicities or even anticipate the side effects. It further opens the door for additional venues of clinical research that we hadn’t really considered previously. It’s really a very encouraging time to be a clinical oncologist. My only regret is that it’s coming toward the end of my career.

Transcript Edited for Clarity 
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Transcript: 

Vassiliki Papadimitrakopoulou, MD: I am very excited about the opportunities for research in patients who are immunotherapy-exposed. We’re seeing early signals with novel agents trying to transform tumors that are called “too hot” and trying to transform patients’ tumors that are unresponsive to immunotherapy to tumors that are responsive. I’m also very excited about the fact that we’re seeing long progression-free survival, duration of responses, and overall survival for investigational arms in all immunotherapy trials. The hope is that some of these patients will receive long-term benefit, and maybe we can use the term cure for our patients with metastatic disease in the future.

Hossein Borghaei, DO: What I’m really excited about is all the new opportunities we have. Clearly, I’m excited about the I-O/chemotherapy combinations because to me, surprisingly, they’re working really well in terms of clinical efficacy and toxicity. I like that, and I think I can use that in my clinic, and I am using it. I would like to see more immuno-oncology combinations. I want to see if we can push chemotherapy further and further down the line and not have to use it in the up-front setting. I realize we might be years away from a scenario in which everybody gets a very active, well-tolerated I-O/I-O combination. But I think we are beginning to see a partition, so if you have somebody with high tumor mutational burden and low PD-L1 expression, you might want to have the option of I-O/I-O therapy, as opposed to just chemotherapy, and at least discuss that with the patient. If you have a patient who, for whatever reason, is unwilling to get chemotherapy or cannot get chemotherapy, having an I-O/I-O combination is a very legitimate and reasonable option.

I think what we haven’t answered is this question of sequencing. Should everybody get everything up front, or should we still use sequential therapy? Now, whether that’s I-O followed by chemotherapy or chemotherapy followed by I-O, I think this sort of question needs to be answered. If survival is going to be the same, and we can start with an I-O single agent that’s less toxic and as efficacious, then at the time of progression use chemotherapy, and the overall survival is going to be basically the same, why not start with something that’s a little less complicated, a little less toxic, and then sequence the treatment?

I think some of these questions will be answered in the ensuing years, but for now, we’re going to be overwhelmed with a wealth of immuno-oncology combinations that are going to be coming at us in various meetings. Our challenge is to figure out which one is more efficacious, which one is well tolerated, and which one can challenge this I-O plus chemotherapy in the frontline setting.

Corey J. Langer, MD: Immunotherapy has, without question, absolutely transformed our practice. I have to confess, I was an immunotherapy skeptic who was informed on prior experience with other agents that were highly toxic and not particularly efficacious. But the emergence of first nivolumab, then pembrolizumab, then atezolizumab—all strikingly positive in phase III studies in the second-line setting, and now in repeatedly positive trials in the frontline setting, either alone or in combination with chemotherapy—has absolutely altered how we practice medical oncology in the thoracic clinic, and only for the better. The patients are the ultimate beneficiaries. As time goes on, our learning curve improves, and we’re better able to manage the toxicities or even anticipate the side effects. It further opens the door for additional venues of clinical research that we hadn’t really considered previously. It’s really a very encouraging time to be a clinical oncologist. My only regret is that it’s coming toward the end of my career.

Transcript Edited for Clarity 
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TitleExpiration DateCME Credits
Community Practice Connections™: Oncology Best Practice™ Decision Points in Advanced NSCLC: Assessing Treatment Options Beyond Disease ProgressionNov 30, 20181.0
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
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