Susan F. Slovin, MD, PhD
Advancements in immunotherapy in the field of prostate cancer have been slow ever since the FDA approval of sipuleucel-T (Provenge) several years ago.
“It’s an exceptionally challenging area. After the success of sipuleucel-T, there have been combinatorial approaches using radiopharmaceuticals, such as radium-223, the checkpoint inhibitor ipilimumab (Yervoy), as well as some chemotherapy regimens,” says Susan F. Slovin, MD, PhD.
In an interview with OncLive
at the 2017 Interdisciplinary Prostate Cancer Congress, Slovin, a medical oncologist at Memorial Sloan Kettering Cancer Center, offered her expert insight on the current state of immunotherapy in prostate cancer.
OncLive: Can you give an overview of your talk on immunotherapy in prostate cancer?
Prostate cancer was among the first solid tumors to have a positive experience with immunotherapy. Until that time, I don’t believe that any solid tumor malignancy—whether it was kidney cancer, prostate cancer, or lung cancer—had any sort of success with an immune approach. For the last 30 years, we’ve seen a variety of different platforms of immunotherapy, including vaccine and viral vectors, none of which showed any impact on prostate cancer.
With the FDA approval of sipuleucel-T, this represented the first successful immunotherapy that showed a survival benefit for a solid tumor, which happened to be prostate cancer. All approaches that have been done subsequently are trying to look at other ways of using the body's immune system to fight the cancer.
What agents are being investigated in this space?
It's an exceptionally challenging area. After the success of sipuleucel-T, there have been combinatorial approaches using radiopharmaceuticals, such as radium-223, the checkpoint inhibitor ipilimumab, as well as some chemotherapy regimens.
More recently, the checkpoint inhibitors have been extremely interesting. There have been at least 3 phase I and II trials of the CTLA-4 inhibitor ipilimumab. The original phase I and II trial was done with and without radiation and gave a signal that perhaps there was some long-term durable responses, although not without autoimmune events, such as hypothyroidism and rashes. This is all thought to be an on-target effect of these antibodies.
What’s happened is that 2 phase III trials—1 prechemotherapy and 1 post-chemotherapy—have not shown or confirmed an overall survival benefit. While there have been several long-term responses, neither trial confirmed ipilimumab to be a standard of care in patients with castrate-resistant metastatic disease who either have or have not received chemotherapy, particularly docetaxel.
Overall, where would you say immunotherapy is at this point in prostate cancer?
We have made tremendous strides looking at different immune-based platforms, which is 1 of the benefits that I'm seeing now. There is a suggestion now that the anti–PD-1 agent pembrolizumab (Keytruda) may be generating a signal in patients with much more end-stage disease, particularly those with visceral metastases. It's interesting, because in 1 of the early phase III trials, this metastasis was thought to be an adverse prognostic indicator to the fact that people would not do well. However, using anti–PD-1 surprisingly ended up resulting in some patients having significant declines in PSA and radiographic improvement.
Other approaches being evaluated include the PROSTVAC platform, which is a transgene of PSA in a fowlpox vector given with 3 immune stimulatory molecules. Then you have these new checkpoint inhibitors, as well as a variety of other molecules to which immunotherapies are being developed, including molecules we call VISTA, LAG-3, FoxP3.
There are a lot of new targets—it’s just that we're waiting, because it takes a while for the immunotherapies to kick in. They don’t work immediately, hence the delay in development.
What would you want the main takeaways to be from your talk?
The takeaway message is that people go through the various treatments over a time as their disease transforms in a dynamic process. We should be collecting tissues, blood, plasma, and circulating tumor cells—all of this is going to be helpful in looking at our ability to correlate certain changes with the treatments that patients are getting.