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Checkpoint Inhibitors for Malignant Pleural Mesothelioma

Panelists: Mary Jo Fidler, MD, Rush; Roy S. Herbst, MD, PhD, Yale ; Geoffrey R. Oxnard, MD, Harvard; Naiyer Rizvi, MD, Columbia; Mark A. Socinski, MD,
Published: Wednesday, Nov 25, 2015


Transcript:

Mark A. Socinski, MD:
Before we end today’s discussion, let’s talk about using checkpoint inhibitors in patients with malignant pleural mesothelioma. I’m going to ask Naiyer to summarize those data. We talked about bevacizumab being an advance in the first-line setting. This is still a disease where after first-line therapy we don’t have a lot of great options. What are your thoughts about this disease and immunotherapy?

Naiyer Rizvi, MD: I think that there are data to come. Tremelimumab was the anti-CTLA-4 agent that showed clear responses in mesothelioma. There’s a randomized trial which is in process with tremelimumab.

Mark A. Socinski, MD: An orphan drug designation?

Naiyer Rizvi, MD: Yes, and certainly the most recent data for pembrolizumab showed that in the PD-L1-positive patients, which was about half of mesothelioma, there was about a 20% response rate. Mesothelioma is another interesting story because it’s also associated with a carcinogen, asbestos exposure, but they are not very mutated tumors. They have a relatively low mutation burden, so biologically they’re quite different. But, I think, there’s clearly activity using pembrolizumab.

Mark A. Socinski, MD: I think those were some of the more exciting data in mesothelioma. The bevacizumab data we talked about, but this was encouraging.

Roy S. Herbst, MD, PhD: From AACR this year, it was very exciting! I’ve talked to patients about it since then and we just need to find trials.

Mark A. Socinski, MD: It’s important to reinforce that most everything that we do in practice has some basis in a clinical trial; either the data have driven our decision-making or they have shaped the way we think of populations of patients outside of the clinical trial. The best treatment option that a patient has is treatment in a clinical trial.

I point out to my patients, very often, that my standard of care recommendation has come from a number of trials that have been done over the years by some of us and by our prior colleagues. The concept of and the commitment to clinical trials are important to what we do in oncology. There’s certainly, in immunotherapy, no lack of trials.

Geoff made this point earlier that there are a number of agents in development, so patients should have access to these. I have found that since ASCO, almost every new patient I see comes in with the word nivolumab written on a piece of paper. So, I think it’s important to reinforce this concept of clinical trials.

Geoffrey R. Oxnard, MD: Right, and the clinical trials are why we’re making a difference and making changes in lung cancer!

Naiyer Rizvi, MD: One clinical challenge has been what to do with the patient that comes in with an autoimmune history. Every week this comes up and I’d be interested to know what people’s approaches are.

Geoffrey R. Oxnard, MD: There’s a clinical trial being developed to answer that exact question.

Roy S. Herbst, MD, PhD: Two questions—I want to comment on the trials but to Naiyer’s point, you have to ask, when someone comes in with a history of an autoimmunity, how serious it was. If they’ve had rheumatoid arthritis, how serious was it? Was the patient on steroids? Is the patient on steroids now? Because I think, at some point, as these drugs are approved in clinical practice, we’ll have to use our judgment. We’ll have to look at the other options.

Geoffrey R. Oxnard, MD: I have a patient who was found, while screened for an anti-PD-1 study, to be positive for hepatitis C. Of course, looking at the literature you’ll see that nivolumab is being developed as a therapy for hepatitis C with some effect.

Mark A. Socinski, MD: But they’re excluded from the trial.

Mary Jo Fidler, MD: They’re excluded from the trial. I saw that last week.

Geoffrey R. Oxnard, MD: I’ll say, I treated him off-label and he did okay.

Naiyer Rizvi, MD: That’s probably okay because there are hepatocellular carcinoma data.

Geoffrey R. Oxnard, MD: My point is that we’re pushing the boundary here, and we all need to do that and describe our experiences as we do it.

Roy S. Herbst, MD, PhD: I will say that for clinical trials, the Lung Master Protocols that are out there are an important component, as well, and many of us are involved with those. Most patients in this country are treated in the community; we need to make sure there are clinical trials that can be done in the community setting.

The Lung Master Protocol, for example, in squamous-cell lung cancer, is looking at genetic drivers. However, we also have two arms now that will receive immunotherapy, either ipilimumab and nivolumab or nivolumab. We’re taking that combination out to the community. I think that’s really important because there will be an immunotherapy clinical trial for a patient who doesn’t have a genetic driver.

We’re also looking at tremelimumab plus MEDI4736 (durvalumab). So, we have trials now that we’re seeding at 500+ sites around the country. It’s important that we have trials that are community-ready for patients to go on them.

Naiyer Rizvi, MD: I think that trial is answering a question, which patients ask me every day: If I progress on nivolumab, will the immunotherapy combination work? We don’t know yet, so I think that trial will be useful.

Roy S. Herbst, MD, PhD: It’s just the tip of the iceberg because there are so many other immune inhibitors which we probably don’t have time to talk about, but it’s an exciting field and the science is going to drive things. Clinical trials and clinical trials with biopsies will really help us to figure out what’s next.

Mark A. Socinski, MD: Often the number one reason a patient doesn’t go on a clinical trial is because they say their doctor didn’t recommend a clinical trial. It comes back to us in doing that.
 
Transcript Edited for Clarity
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Transcript:

Mark A. Socinski, MD:
Before we end today’s discussion, let’s talk about using checkpoint inhibitors in patients with malignant pleural mesothelioma. I’m going to ask Naiyer to summarize those data. We talked about bevacizumab being an advance in the first-line setting. This is still a disease where after first-line therapy we don’t have a lot of great options. What are your thoughts about this disease and immunotherapy?

Naiyer Rizvi, MD: I think that there are data to come. Tremelimumab was the anti-CTLA-4 agent that showed clear responses in mesothelioma. There’s a randomized trial which is in process with tremelimumab.

Mark A. Socinski, MD: An orphan drug designation?

Naiyer Rizvi, MD: Yes, and certainly the most recent data for pembrolizumab showed that in the PD-L1-positive patients, which was about half of mesothelioma, there was about a 20% response rate. Mesothelioma is another interesting story because it’s also associated with a carcinogen, asbestos exposure, but they are not very mutated tumors. They have a relatively low mutation burden, so biologically they’re quite different. But, I think, there’s clearly activity using pembrolizumab.

Mark A. Socinski, MD: I think those were some of the more exciting data in mesothelioma. The bevacizumab data we talked about, but this was encouraging.

Roy S. Herbst, MD, PhD: From AACR this year, it was very exciting! I’ve talked to patients about it since then and we just need to find trials.

Mark A. Socinski, MD: It’s important to reinforce that most everything that we do in practice has some basis in a clinical trial; either the data have driven our decision-making or they have shaped the way we think of populations of patients outside of the clinical trial. The best treatment option that a patient has is treatment in a clinical trial.

I point out to my patients, very often, that my standard of care recommendation has come from a number of trials that have been done over the years by some of us and by our prior colleagues. The concept of and the commitment to clinical trials are important to what we do in oncology. There’s certainly, in immunotherapy, no lack of trials.

Geoff made this point earlier that there are a number of agents in development, so patients should have access to these. I have found that since ASCO, almost every new patient I see comes in with the word nivolumab written on a piece of paper. So, I think it’s important to reinforce this concept of clinical trials.

Geoffrey R. Oxnard, MD: Right, and the clinical trials are why we’re making a difference and making changes in lung cancer!

Naiyer Rizvi, MD: One clinical challenge has been what to do with the patient that comes in with an autoimmune history. Every week this comes up and I’d be interested to know what people’s approaches are.

Geoffrey R. Oxnard, MD: There’s a clinical trial being developed to answer that exact question.

Roy S. Herbst, MD, PhD: Two questions—I want to comment on the trials but to Naiyer’s point, you have to ask, when someone comes in with a history of an autoimmunity, how serious it was. If they’ve had rheumatoid arthritis, how serious was it? Was the patient on steroids? Is the patient on steroids now? Because I think, at some point, as these drugs are approved in clinical practice, we’ll have to use our judgment. We’ll have to look at the other options.

Geoffrey R. Oxnard, MD: I have a patient who was found, while screened for an anti-PD-1 study, to be positive for hepatitis C. Of course, looking at the literature you’ll see that nivolumab is being developed as a therapy for hepatitis C with some effect.

Mark A. Socinski, MD: But they’re excluded from the trial.

Mary Jo Fidler, MD: They’re excluded from the trial. I saw that last week.

Geoffrey R. Oxnard, MD: I’ll say, I treated him off-label and he did okay.

Naiyer Rizvi, MD: That’s probably okay because there are hepatocellular carcinoma data.

Geoffrey R. Oxnard, MD: My point is that we’re pushing the boundary here, and we all need to do that and describe our experiences as we do it.

Roy S. Herbst, MD, PhD: I will say that for clinical trials, the Lung Master Protocols that are out there are an important component, as well, and many of us are involved with those. Most patients in this country are treated in the community; we need to make sure there are clinical trials that can be done in the community setting.

The Lung Master Protocol, for example, in squamous-cell lung cancer, is looking at genetic drivers. However, we also have two arms now that will receive immunotherapy, either ipilimumab and nivolumab or nivolumab. We’re taking that combination out to the community. I think that’s really important because there will be an immunotherapy clinical trial for a patient who doesn’t have a genetic driver.

We’re also looking at tremelimumab plus MEDI4736 (durvalumab). So, we have trials now that we’re seeding at 500+ sites around the country. It’s important that we have trials that are community-ready for patients to go on them.

Naiyer Rizvi, MD: I think that trial is answering a question, which patients ask me every day: If I progress on nivolumab, will the immunotherapy combination work? We don’t know yet, so I think that trial will be useful.

Roy S. Herbst, MD, PhD: It’s just the tip of the iceberg because there are so many other immune inhibitors which we probably don’t have time to talk about, but it’s an exciting field and the science is going to drive things. Clinical trials and clinical trials with biopsies will really help us to figure out what’s next.

Mark A. Socinski, MD: Often the number one reason a patient doesn’t go on a clinical trial is because they say their doctor didn’t recommend a clinical trial. It comes back to us in doing that.
 
Transcript Edited for Clarity
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