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Phase II EMPOWER-CSCC 1 Trial

Insights From: Robert L. Ferris, MD, PhD, UPMC Hillman Cancer Center; Anna C. Pavlick, DO, NYU Langone Hospitals; Todd E. Schlesinger, MD, FAAD, FASMS, Dermatology & Laser Center of Charleston
Published: Tuesday, Feb 26, 2019



Transcript: 

Anna C. Pavlick, DO:
Well, the implications of the phase II registrational trial that was done really changed our ability to impact patients’ lives and their survival, keeping in mind that all the prior therapies we had access to provided palliation with limited disease control. Looking at the results of the cemiplimab trial, these patients have a very high response rate, better than 50%. But what we see even more importantly is that there’s a plateau on the response line. So that plateau indicates that these patients are having long-term durable responses that we’re hoping translate into cure for these patients.

Todd E. Schlesinger, MD, FAAD, FASMS: So real-life therapy versus systemic therapy based the on EMPOWER-CSCC 1 study. The EMPOWER study gave us some very good information about cemiplimab, the approved therapy for cutaneous squamous cell carcinoma [CSCC]. It told us that there is a therapy that you can be given by intravenous [IV] infusion that is effective. It told us that the time to start seeing a response can be under 2 months. It also told us that we can get an overall response rate approaching 50%, and a durable response rate approaching 60%. So these are things that we didn’t have before. We were unable to provide this type of therapy, there was nothing approved. There were other systemic therapies approved for squamous cell carcinoma, but not for cutaneous, per se, similar therapy.

You know with an approved option we certainly have more choices now, and we can offer this to our patients to at least give them another choice besides either disfiguring surgery and/or radiation that may or may not cause them some morbidity down the road. So it’s nice to see some of this data. Of course, we’d be looking for longer-term data as more patients are exposed to the medication. Over time hopefully we’ll see some improved outcomes. As far as the adverse events go, they seem to be manageable based on the trial data that we’ve seen so far, so that’s always good to see as well.

The EMPOWER study taught us some things about how we refer patients for systemic therapy versus real life. In studies, which are very well controlled, the subjects that are enrolled are usually of a more severe type. So more advanced cases of squamous cell carcinoma. These patients have also been exposed to radiation therapy before and maybe not done well. So the criteria are higher for a trial. We learned in the trial that the overall response rate was approximately 50% for the patients that were enrolled in the trial. We also learned that the durable response rate was almost 60%.

The last thing we learned was that the time to response was pretty short, at about 2 months or so. So what does that tell me? I think that tells me for my community-based practice that there are patients in my practice that could benefit from going on IV cemiplimab, or the approved medication for cutaneous squamous cell carcinoma that may not be quite as severe as the trial subjects were.

So I would consider that a patient with advanced squamous cell carcinoma that we consider unresectable, or maybe would cause a lot of morbidity for the patients to remove that tumor. Maybe the patient would have damage to a critical structure or they would have a large cosmetic deficit, or if, of course they’ve been diagnosed with metastases of any kind, certainly this would be an option for us.
Basically the bottom line is real-world versus trial. Trial subjects are typically, especially in this case, more severe subjects. So we might consider it for a broader range of patients in our practice versus the subjects in the trial.

Robert L. Ferris, MD, PhD: Whenever patients are enrolled in a clinical trial the eligibility has to be more focused. When we get into the real world, then I think it depends on the environment that patient is seeing, is it a comprehensive cancer center where there’s already a multidisciplinary team, and we evaluate our aggressive cancers of all types for trial eligibility all the time. In more of a community setting my guess is that it’s different than the clinical trials. Whereas at our center we were already adhering to those kind of eligibility categories of the unresectable population, the recurrent metastatic. We don’t segregate them, of course, like a clinical trial expansion cohort did. But we have a multidisciplinary treatment team that assesses for eligibility along the way.

Now once a therapy becomes FDA approved and one can use it in standard practice, then the combinations and the more innovative ways to look at its combination with radiation, or potentially with cetuximab, because both may be FDA approved, and then the oncology team can begin integrating it into conventional approved therapies, and that’s where we are.

Anna C. Pavlick, DO: Any time that you conduct a clinical trial the criteria for enrollment are very stringent, again because you need to factor out complicating factors such as autoimmune diseases. And many older patients will have an underlying autoimmune disease whether it’s CLL [chronic lymphocytic leukemia], whether it’s rheumatoid arthritis, whether it’s psoriasis. So those patients were excluded because you have to in order to really tease out what’s the toxicity and how well patients will do.

So using these drugs in the real world, those are clearly not going to be rate-limiting factors, you just need to be aware that when you treat patients who have underlying autoimmune diseases, these medicines, like the other PD-1 [programmed cell death protein 1] inhibitors, are going to exacerbate those symptoms, and you have to work as a team and work with the rheumatologists to either control the rash or control the joint pain. But you can easily treat these patients and manage their adverse effects at the same time.

The long-term efficacy and safety data are really not long term. The trial has been closed now for a year-and-a-half, and so that’s your long-term safety data. But, at a year-and-a-half, again the responses are at 50%. We’re not seeing any long-term adverse events. We do know like all the other immunotherapies, if a patient develops an endocrinopathy like hypothyroidism, which is the one that was most commonly seen in the cemiplimab trial, the hypothyroidism is usually permanent and needs to be treated with thyroid replacement medication for the remainder of the patient’s life.

Transcript edited for clarity.
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Transcript: 

Anna C. Pavlick, DO:
Well, the implications of the phase II registrational trial that was done really changed our ability to impact patients’ lives and their survival, keeping in mind that all the prior therapies we had access to provided palliation with limited disease control. Looking at the results of the cemiplimab trial, these patients have a very high response rate, better than 50%. But what we see even more importantly is that there’s a plateau on the response line. So that plateau indicates that these patients are having long-term durable responses that we’re hoping translate into cure for these patients.

Todd E. Schlesinger, MD, FAAD, FASMS: So real-life therapy versus systemic therapy based the on EMPOWER-CSCC 1 study. The EMPOWER study gave us some very good information about cemiplimab, the approved therapy for cutaneous squamous cell carcinoma [CSCC]. It told us that there is a therapy that you can be given by intravenous [IV] infusion that is effective. It told us that the time to start seeing a response can be under 2 months. It also told us that we can get an overall response rate approaching 50%, and a durable response rate approaching 60%. So these are things that we didn’t have before. We were unable to provide this type of therapy, there was nothing approved. There were other systemic therapies approved for squamous cell carcinoma, but not for cutaneous, per se, similar therapy.

You know with an approved option we certainly have more choices now, and we can offer this to our patients to at least give them another choice besides either disfiguring surgery and/or radiation that may or may not cause them some morbidity down the road. So it’s nice to see some of this data. Of course, we’d be looking for longer-term data as more patients are exposed to the medication. Over time hopefully we’ll see some improved outcomes. As far as the adverse events go, they seem to be manageable based on the trial data that we’ve seen so far, so that’s always good to see as well.

The EMPOWER study taught us some things about how we refer patients for systemic therapy versus real life. In studies, which are very well controlled, the subjects that are enrolled are usually of a more severe type. So more advanced cases of squamous cell carcinoma. These patients have also been exposed to radiation therapy before and maybe not done well. So the criteria are higher for a trial. We learned in the trial that the overall response rate was approximately 50% for the patients that were enrolled in the trial. We also learned that the durable response rate was almost 60%.

The last thing we learned was that the time to response was pretty short, at about 2 months or so. So what does that tell me? I think that tells me for my community-based practice that there are patients in my practice that could benefit from going on IV cemiplimab, or the approved medication for cutaneous squamous cell carcinoma that may not be quite as severe as the trial subjects were.

So I would consider that a patient with advanced squamous cell carcinoma that we consider unresectable, or maybe would cause a lot of morbidity for the patients to remove that tumor. Maybe the patient would have damage to a critical structure or they would have a large cosmetic deficit, or if, of course they’ve been diagnosed with metastases of any kind, certainly this would be an option for us.
Basically the bottom line is real-world versus trial. Trial subjects are typically, especially in this case, more severe subjects. So we might consider it for a broader range of patients in our practice versus the subjects in the trial.

Robert L. Ferris, MD, PhD: Whenever patients are enrolled in a clinical trial the eligibility has to be more focused. When we get into the real world, then I think it depends on the environment that patient is seeing, is it a comprehensive cancer center where there’s already a multidisciplinary team, and we evaluate our aggressive cancers of all types for trial eligibility all the time. In more of a community setting my guess is that it’s different than the clinical trials. Whereas at our center we were already adhering to those kind of eligibility categories of the unresectable population, the recurrent metastatic. We don’t segregate them, of course, like a clinical trial expansion cohort did. But we have a multidisciplinary treatment team that assesses for eligibility along the way.

Now once a therapy becomes FDA approved and one can use it in standard practice, then the combinations and the more innovative ways to look at its combination with radiation, or potentially with cetuximab, because both may be FDA approved, and then the oncology team can begin integrating it into conventional approved therapies, and that’s where we are.

Anna C. Pavlick, DO: Any time that you conduct a clinical trial the criteria for enrollment are very stringent, again because you need to factor out complicating factors such as autoimmune diseases. And many older patients will have an underlying autoimmune disease whether it’s CLL [chronic lymphocytic leukemia], whether it’s rheumatoid arthritis, whether it’s psoriasis. So those patients were excluded because you have to in order to really tease out what’s the toxicity and how well patients will do.

So using these drugs in the real world, those are clearly not going to be rate-limiting factors, you just need to be aware that when you treat patients who have underlying autoimmune diseases, these medicines, like the other PD-1 [programmed cell death protein 1] inhibitors, are going to exacerbate those symptoms, and you have to work as a team and work with the rheumatologists to either control the rash or control the joint pain. But you can easily treat these patients and manage their adverse effects at the same time.

The long-term efficacy and safety data are really not long term. The trial has been closed now for a year-and-a-half, and so that’s your long-term safety data. But, at a year-and-a-half, again the responses are at 50%. We’re not seeing any long-term adverse events. We do know like all the other immunotherapies, if a patient develops an endocrinopathy like hypothyroidism, which is the one that was most commonly seen in the cemiplimab trial, the hypothyroidism is usually permanent and needs to be treated with thyroid replacement medication for the remainder of the patient’s life.

Transcript edited for clarity.
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