ONCAlert | Upfront Therapy for mRCC

Optimizing Use of I-O Therapy in Non-Melanoma Skin Cancer

Targeted Oncology
Published Online:12:39 PM, Wed July 17, 2019

Shubham Pant, MD: That’s great, Dr Migden. I think I learned a lot. These drugs also have adverse effects. They’re different than cytotoxic, but checkpoint inhibitors do have side effects also. So what should community oncologists look for when they’re giving these therapies as far as adverse effects are concerned?

Michael R. Migden, MD: Community oncologists are probably already aware from other preexisting approved anti–PD-1 [anti–programmed cell death protein 1] therapy and other immunotherapy in various conditions that these anti–PD-1 agents can have immune-related adverse events, and they can become life-threatening. The key is always early recognition and then early intervention. I tell all of my patients, if you have anything that seems even small but different, a new cough, a minor diarrhea, you have to take it seriously. You need to come in and be checked because intervention early is the key to avoid worse complications or risk of death. And it’s typically systemic steroid as the intervention and referral to a specialist, of course.

The other thing to know is that during treatment—especially in locally advanced patients, because the nature of advanced cSCC [cutaneous squamous cell carcinoma] is different from say melanoma or metastatic disease—these tend to be larger lesions, they tend to be very visible, they can be exophytic, so they can have a Z axis, a third dimension. So when immune response does happen, it can be quite brisk.

Because this tumor tends to be a larger and very visible, the dramatic appearance of an active immune response can be concerning, both to the patient who could say, “What the heck’s going on? This is getting worse,” but also to the uninformed clinician who’s maybe not used to seeing such visible lesions on the skin. They might say, “Wow, that’s getting worse,” and that brings up the topic of pseudoprogression. Because pseudoprogression could result when you have a massive influx of activated T cells, at least that’s the belief. And it can appear that the lesion is getting larger, but this apparent increase of size could precede an actual significant decrease in size. So it’s important to recognize that it can happen.

It’s important to think, what can I do to determine whether it’s true progression or pseudoprogression? There are a couple of simple things. The most important I think is to ask the patient, “How do you feel?” Because, when I’ve had this in a couple of patients and you ask them, if the patient says, “I feel great. In fact, I have more energy than I’ve had before and I’m doing more chores and whatever,” that’s a pretty good sign that maybe you should continue treatment and see if it’s going to start regressing. The other thing is after some period, if you think it’s truly getting larger, you can biopsy the area outside the original dimensions, significantly outside. And if you pick up tumor in an area that looked completely normal before, that might favor true progression.

I had a case that during the trial where the tumor started small, it looked cold, there wasn’t much erythema so it didn’t look inflamed, and then started on and after 2 months, the tumor was much larger. So I had to rate the patient as having progressive disease. The phase II study allowed patients with progressive disease to remain on active treatment if it was deemed in their best interest. So that patient said, “I feel great, I want to continue.” Kept the patient going with another 3 months, that now larger area started to melt away. And with an additional 2 months, that area was completely gone. So here you have a case of either delayed response where initially it wasn’t responding, then it grew, and then it did respond, or probably more likely pseudoprogression. And then the patient, because they stayed on treatment, ended up with the lesion completely resolved.

It’s challenging because you don’t want to keep patients on a therapy if they’re truly having progression. You’re getting like hyperprogression. It’s growing fast. You might have to try and go to plan B. But you also don’t want to rob patients from a potential response, so you have to be very thoughtful. I recommend those 2 tools—asking the patient, looking for any other signs that their general condition is deteriorating, and so on.

Shubham Pant, MD: So clinical symptoms are very big, and if any new places pop up, you biopsy to see if that’s the same kind of cancer.

Michael R. Migden, MD: New biopsies, and also perhaps repeat imaging to see if there’s any imaging signs that look more like tumor and less like just inflammatory response.

Shubham Pant, MD: I think that’s really fascinating because normally, when we see scans it’s different. We see scans, liver lesions are getting bigger. It’s not as dramatic as looking at a skin lesion just growing. And that can be a little bit more concerning, at least to the physician and to the patients.

Michael R. Migden, MD: And that’s why there’s definitely a role for a dermatologic oncologist in this multidisciplinary tumor board discussion because a perspective of somebody whose core is skin might be different from somebody whose core is more medicine oncology. They may not have the same feel for these changes when you look at the skin, and that’s a very important thing to keep in your toolboxes. Maybe talk to a dermatologic oncologist if you know one or a Mohs surgeon, saying, “What’s your opinion about the way this looks?”

Transcript edited for clarity.

Shubham Pant, MD: That’s great, Dr Migden. I think I learned a lot. These drugs also have adverse effects. They’re different than cytotoxic, but checkpoint inhibitors do have side effects also. So what should community oncologists look for when they’re giving these therapies as far as adverse effects are concerned?

Michael R. Migden, MD: Community oncologists are probably already aware from other preexisting approved anti–PD-1 [anti–programmed cell death protein 1] therapy and other immunotherapy in various conditions that these anti–PD-1 agents can have immune-related adverse events, and they can become life-threatening. The key is always early recognition and then early intervention. I tell all of my patients, if you have anything that seems even small but different, a new cough, a minor diarrhea, you have to take it seriously. You need to come in and be checked because intervention early is the key to avoid worse complications or risk of death. And it’s typically systemic steroid as the intervention and referral to a specialist, of course.

The other thing to know is that during treatment—especially in locally advanced patients, because the nature of advanced cSCC [cutaneous squamous cell carcinoma] is different from say melanoma or metastatic disease—these tend to be larger lesions, they tend to be very visible, they can be exophytic, so they can have a Z axis, a third dimension. So when immune response does happen, it can be quite brisk.

Because this tumor tends to be a larger and very visible, the dramatic appearance of an active immune response can be concerning, both to the patient who could say, “What the heck’s going on? This is getting worse,” but also to the uninformed clinician who’s maybe not used to seeing such visible lesions on the skin. They might say, “Wow, that’s getting worse,” and that brings up the topic of pseudoprogression. Because pseudoprogression could result when you have a massive influx of activated T cells, at least that’s the belief. And it can appear that the lesion is getting larger, but this apparent increase of size could precede an actual significant decrease in size. So it’s important to recognize that it can happen.

It’s important to think, what can I do to determine whether it’s true progression or pseudoprogression? There are a couple of simple things. The most important I think is to ask the patient, “How do you feel?” Because, when I’ve had this in a couple of patients and you ask them, if the patient says, “I feel great. In fact, I have more energy than I’ve had before and I’m doing more chores and whatever,” that’s a pretty good sign that maybe you should continue treatment and see if it’s going to start regressing. The other thing is after some period, if you think it’s truly getting larger, you can biopsy the area outside the original dimensions, significantly outside. And if you pick up tumor in an area that looked completely normal before, that might favor true progression.

I had a case that during the trial where the tumor started small, it looked cold, there wasn’t much erythema so it didn’t look inflamed, and then started on and after 2 months, the tumor was much larger. So I had to rate the patient as having progressive disease. The phase II study allowed patients with progressive disease to remain on active treatment if it was deemed in their best interest. So that patient said, “I feel great, I want to continue.” Kept the patient going with another 3 months, that now larger area started to melt away. And with an additional 2 months, that area was completely gone. So here you have a case of either delayed response where initially it wasn’t responding, then it grew, and then it did respond, or probably more likely pseudoprogression. And then the patient, because they stayed on treatment, ended up with the lesion completely resolved.

It’s challenging because you don’t want to keep patients on a therapy if they’re truly having progression. You’re getting like hyperprogression. It’s growing fast. You might have to try and go to plan B. But you also don’t want to rob patients from a potential response, so you have to be very thoughtful. I recommend those 2 tools—asking the patient, looking for any other signs that their general condition is deteriorating, and so on.

Shubham Pant, MD: So clinical symptoms are very big, and if any new places pop up, you biopsy to see if that’s the same kind of cancer.

Michael R. Migden, MD: New biopsies, and also perhaps repeat imaging to see if there’s any imaging signs that look more like tumor and less like just inflammatory response.

Shubham Pant, MD: I think that’s really fascinating because normally, when we see scans it’s different. We see scans, liver lesions are getting bigger. It’s not as dramatic as looking at a skin lesion just growing. And that can be a little bit more concerning, at least to the physician and to the patients.

Michael R. Migden, MD: And that’s why there’s definitely a role for a dermatologic oncologist in this multidisciplinary tumor board discussion because a perspective of somebody whose core is skin might be different from somebody whose core is more medicine oncology. They may not have the same feel for these changes when you look at the skin, and that’s a very important thing to keep in your toolboxes. Maybe talk to a dermatologic oncologist if you know one or a Mohs surgeon, saying, “What’s your opinion about the way this looks?”

Transcript edited for clarity.
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