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Second-Line Therapies for Non-Driver 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: Friday, Apr 22, 2016


Transcript:

Mark A. Socinski, MD:
Let me ask Dr. Weiss. Up until recently, we talked a little bit about bevacizumab in the first-line setting. A little over a year ago, we had the approval of ramucirumab: different antibody, different mechanism of action, different setting. Just walk us through your thoughts about ramucirumab.

Jared Weiss, MD: To be honest, my main thoughts about ramucirumab are more about the drug that it’s combined with, docetaxel. Dr. Levy brought up the point that patients may be moving more into later lines and may be more receptive to clinical trials with some of these changes. I think it’s extremely relevant that our trials are more likely to work than they historically were and less likely to be toxic than they were in the past, as we’re increasingly speaking about targeted agents and immunotherapeutic agents. That changes the whole calculus. It also changes the whole calculus about how I think about this drug. When added to docetaxel, there is a small but real survival advantage with the use of ramucirumab, and certainly when I use docetaxel, it’s an option that I prefer. But the main point impacting more of my patients is my preference to avoid docetaxel, which I see as one of [the] most toxic of our cytotoxic agents.

Mark A. Socinski, MD: Part of why ramucirumab has suffered a little bit in terms of its uptake has been ASCO imposing these clinically meaningful benefits. We had a statistically significant trial. It got approved by the FDA, but yet it’s kind of in that zone. Where is the bang worth the buck, so to speak? Greg, any thoughts on this?

Gregory J. Riely, MD, PhD: I think the other factor that gets thrown into this is the notion of value and whether we’re spending too much on cancer care in general. And it gets to be a very complicated story. And I think you’re right, that when the initial presentation came out of ramucirumab, people were generally underwhelmed; they expected more. But I have to say I’ve seen, among my colleagues and in the referrals I get, a fair amount more usage of ramucirumab than I was expecting to see. And I think it’s really taken hold in the setting where you decided that you’re going to give docetaxel, you decided you’re going to accept that toxicity profile. The additional toxicity associated with ramucirumab is modest, and so I think people feel more comfortable using it.

Mark A. Socinski, MD: So, Tom, I want to get back to the first-line choices because we recently had an approval of another antibody; in this case, necitumumab in the squamous carcinoma space. There was a trial very similar to the ramucirumab REVEL trial, where we had about the same amount of benefit. It is now FDA-approved, but falls in that zone of how clinically meaningful is this relative to the cost and all these sorts of things? Your thoughts on necitumumab?

Thomas E. Stinchcombe, MD: I think it does provide a modest but real survival benefit. I think it’s combined with cisplatin/gemcitabine. I would see this, in my practice, as being the young squamous patient without comorbidities who wants to be aggressive, and use it in that setting. I’ll probably remain tied to the cisplatin/gemcitabine backbone because that is the FDA approval and that does sort of limit your patient population.

Mark A. Socinski, MD: It does limit the population, yes.

Jared Weiss, MD: And that’s been my limitation as well: extreme aversion to the use of cisplatin in the stage IV patient. It’s quite a bit more toxic even if we had been able to ameliorate some of that with modern antiemetics and nephroprotective strategies.

Mark A. Socinski, MD: But it seems like in this population—compared to the oncogenic-driver population—that the impact we’ve had, even though it’s been real, it’s been very modest. But I have to believe that once you start adding up these incremental benefits, at the end of the day, we are helping patients not only with palliation, but with prolongation of survival.

Benjamin P. Levy, MD: I think we need to make one point in the context of what’s considered value or clinically meaningful. Very few lung cancer trials, at least up until recently, have shown survival advantages. So for those that do, I think we need to keep those drugs in mind. We don’t see survival advantages that much in lung cancer trials. In fact, if you were to look in the past 20 years, about 5% ever show any sort of meaningful benefit. So I think we need to remember that. Even though there are metrics set by ASCO that may seem reasonable, we need to remember that with these drugs, it’s rare that we see these type of survival advantages.

Mark A. Socinski, MD: And, honestly, I’d like to hear the patient’s voice about the benefit, because I think once you have cancer, the marginal benefit looks probably better than when you don’t have cancer. I think that’s an area that’s relatively understudied. What do patients think is clinically meaningful? Not what does ASCO think is clinically meaningful or what do policy makers think is clinically meaningful.

Gregory J. Riely, MD, PhD: And I think what goes along with that is the patient’s perception of the toxicities. A drug that leads to a short overall survival, but doesn’t lead to any apparent toxicity, versus a drug that leads to short improvement in overall survival, but gives them a rash. How does a patient balance that?

Transcript Edited for Clarity
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Transcript:

Mark A. Socinski, MD:
Let me ask Dr. Weiss. Up until recently, we talked a little bit about bevacizumab in the first-line setting. A little over a year ago, we had the approval of ramucirumab: different antibody, different mechanism of action, different setting. Just walk us through your thoughts about ramucirumab.

Jared Weiss, MD: To be honest, my main thoughts about ramucirumab are more about the drug that it’s combined with, docetaxel. Dr. Levy brought up the point that patients may be moving more into later lines and may be more receptive to clinical trials with some of these changes. I think it’s extremely relevant that our trials are more likely to work than they historically were and less likely to be toxic than they were in the past, as we’re increasingly speaking about targeted agents and immunotherapeutic agents. That changes the whole calculus. It also changes the whole calculus about how I think about this drug. When added to docetaxel, there is a small but real survival advantage with the use of ramucirumab, and certainly when I use docetaxel, it’s an option that I prefer. But the main point impacting more of my patients is my preference to avoid docetaxel, which I see as one of [the] most toxic of our cytotoxic agents.

Mark A. Socinski, MD: Part of why ramucirumab has suffered a little bit in terms of its uptake has been ASCO imposing these clinically meaningful benefits. We had a statistically significant trial. It got approved by the FDA, but yet it’s kind of in that zone. Where is the bang worth the buck, so to speak? Greg, any thoughts on this?

Gregory J. Riely, MD, PhD: I think the other factor that gets thrown into this is the notion of value and whether we’re spending too much on cancer care in general. And it gets to be a very complicated story. And I think you’re right, that when the initial presentation came out of ramucirumab, people were generally underwhelmed; they expected more. But I have to say I’ve seen, among my colleagues and in the referrals I get, a fair amount more usage of ramucirumab than I was expecting to see. And I think it’s really taken hold in the setting where you decided that you’re going to give docetaxel, you decided you’re going to accept that toxicity profile. The additional toxicity associated with ramucirumab is modest, and so I think people feel more comfortable using it.

Mark A. Socinski, MD: So, Tom, I want to get back to the first-line choices because we recently had an approval of another antibody; in this case, necitumumab in the squamous carcinoma space. There was a trial very similar to the ramucirumab REVEL trial, where we had about the same amount of benefit. It is now FDA-approved, but falls in that zone of how clinically meaningful is this relative to the cost and all these sorts of things? Your thoughts on necitumumab?

Thomas E. Stinchcombe, MD: I think it does provide a modest but real survival benefit. I think it’s combined with cisplatin/gemcitabine. I would see this, in my practice, as being the young squamous patient without comorbidities who wants to be aggressive, and use it in that setting. I’ll probably remain tied to the cisplatin/gemcitabine backbone because that is the FDA approval and that does sort of limit your patient population.

Mark A. Socinski, MD: It does limit the population, yes.

Jared Weiss, MD: And that’s been my limitation as well: extreme aversion to the use of cisplatin in the stage IV patient. It’s quite a bit more toxic even if we had been able to ameliorate some of that with modern antiemetics and nephroprotective strategies.

Mark A. Socinski, MD: But it seems like in this population—compared to the oncogenic-driver population—that the impact we’ve had, even though it’s been real, it’s been very modest. But I have to believe that once you start adding up these incremental benefits, at the end of the day, we are helping patients not only with palliation, but with prolongation of survival.

Benjamin P. Levy, MD: I think we need to make one point in the context of what’s considered value or clinically meaningful. Very few lung cancer trials, at least up until recently, have shown survival advantages. So for those that do, I think we need to keep those drugs in mind. We don’t see survival advantages that much in lung cancer trials. In fact, if you were to look in the past 20 years, about 5% ever show any sort of meaningful benefit. So I think we need to remember that. Even though there are metrics set by ASCO that may seem reasonable, we need to remember that with these drugs, it’s rare that we see these type of survival advantages.

Mark A. Socinski, MD: And, honestly, I’d like to hear the patient’s voice about the benefit, because I think once you have cancer, the marginal benefit looks probably better than when you don’t have cancer. I think that’s an area that’s relatively understudied. What do patients think is clinically meaningful? Not what does ASCO think is clinically meaningful or what do policy makers think is clinically meaningful.

Gregory J. Riely, MD, PhD: And I think what goes along with that is the patient’s perception of the toxicities. A drug that leads to a short overall survival, but doesn’t lead to any apparent toxicity, versus a drug that leads to short improvement in overall survival, but gives them a rash. How does a patient balance that?

Transcript Edited for Clarity
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