ONCAlert | Upfront Therapy for mRCC

Case Study: Urothelial Carcinoma/Angiosarcoma

Targeted Oncology
Published Online:12:48 PM, Wed May 8, 2019

Arlene O. Siefker-Radtke, MD: With the large number of patients that I’ve treated with the combination of bempegaldesleukin plus nivolumab, currently I think it’s over 25 to 30, we have also observed some unusual pseudoprogression of other diseases. But if you look at the next set of slides, this is a patient who had a stage IV urothelial cancer, and when they presented for treatment they also reported having this small flaky nodule that had been present on their cheek, and it had been there waxing and waning for over a year. It was not causing him any significant adverse effects whatsoever.

And I’ll be honest, in a patient with a stage IV incurable bladder cancer, for which the typical survival is estimated to be around 15 months, on average, with current standard-of-care treatment, I tend to not worry about cosmetic or dermatologic effects. These are people who typically die of their disease quite quickly without aggressive therapy.

This patient was enrolled on the combination of bempegaldesleukin plus nivolumab, and a few days after his infusion called us saying this nodule in his cheek had grown significantly. Unfortunately, I don’t have a baseline photo, but he returned to see us in clinic, and we saw significant growth in this nodule with a lot of erythema. And the erythema was extending up to his lower eyelid, along his nares, and down to his lip, suggesting that there was a process going on in this area that we had previously not recognized.

We sent him to dermatology and did a biopsy, and he was diagnosed with an angiosarcoma. When I discussed the case with our angiosarcoma experts, they said these nodules typically underrepresent the true extent of disease. And when they go into resect, these angiosarcomas of the face, what they initially perceive as a small procedure typically extends to more extensive resections. That can have a major impact on those patients.

As a result of treatment, the nodule increased again—consistent with this type of pseudoprogression  due to the immune response—driving immune cells into the tumor. But as you can see, over time this nodule improved. And as of the time of this presentation, he appears in a clinical complete remission with no nodularity remaining on his cheek.

As a result, there are trials studying this combination of bempegaldesleukin, with nivolumab in patients with angiosarcoma as well.

The combination’s being studied in many tumor types—lung cancer, kidney cancer, melanoma, bladder cancer—and they have multiple cohorts accruing in other disease states to decide whether if they should do larger trials as well. So I think it is a truly exciting combination based on the activity observed across disease sites.

When you look at the setting of melanoma, the complete response rate of bempegaldesleukin plus nivolumab that was recently reported was 24% complete responses, which is definitely better than what has been observed with single-agent immunotherapy. So there are a lot of reasons why people are excited about this combination and are interested in studying it across disease states.

Transcript edited for clarity.

Arlene O. Siefker-Radtke, MD: With the large number of patients that I’ve treated with the combination of bempegaldesleukin plus nivolumab, currently I think it’s over 25 to 30, we have also observed some unusual pseudoprogression of other diseases. But if you look at the next set of slides, this is a patient who had a stage IV urothelial cancer, and when they presented for treatment they also reported having this small flaky nodule that had been present on their cheek, and it had been there waxing and waning for over a year. It was not causing him any significant adverse effects whatsoever.

And I’ll be honest, in a patient with a stage IV incurable bladder cancer, for which the typical survival is estimated to be around 15 months, on average, with current standard-of-care treatment, I tend to not worry about cosmetic or dermatologic effects. These are people who typically die of their disease quite quickly without aggressive therapy.

This patient was enrolled on the combination of bempegaldesleukin plus nivolumab, and a few days after his infusion called us saying this nodule in his cheek had grown significantly. Unfortunately, I don’t have a baseline photo, but he returned to see us in clinic, and we saw significant growth in this nodule with a lot of erythema. And the erythema was extending up to his lower eyelid, along his nares, and down to his lip, suggesting that there was a process going on in this area that we had previously not recognized.

We sent him to dermatology and did a biopsy, and he was diagnosed with an angiosarcoma. When I discussed the case with our angiosarcoma experts, they said these nodules typically underrepresent the true extent of disease. And when they go into resect, these angiosarcomas of the face, what they initially perceive as a small procedure typically extends to more extensive resections. That can have a major impact on those patients.

As a result of treatment, the nodule increased again—consistent with this type of pseudoprogression  due to the immune response—driving immune cells into the tumor. But as you can see, over time this nodule improved. And as of the time of this presentation, he appears in a clinical complete remission with no nodularity remaining on his cheek.

As a result, there are trials studying this combination of bempegaldesleukin, with nivolumab in patients with angiosarcoma as well.

The combination’s being studied in many tumor types—lung cancer, kidney cancer, melanoma, bladder cancer—and they have multiple cohorts accruing in other disease states to decide whether if they should do larger trials as well. So I think it is a truly exciting combination based on the activity observed across disease sites.

When you look at the setting of melanoma, the complete response rate of bempegaldesleukin plus nivolumab that was recently reported was 24% complete responses, which is definitely better than what has been observed with single-agent immunotherapy. So there are a lot of reasons why people are excited about this combination and are interested in studying it across disease states.

Transcript edited for clarity.
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