The Rise of Immunotherapy in Prostate Cancer

In part six of this roundtable series, Drs. Irbaz B. Riaz, Chad Cherington, Roopesh Kantala, and James Ewing finish their discussion by reviewing immunotherapy in prostate cancer, along with T-cell engagers and how they compare to BiTE therapies. The panelists also discuss sequencing and new treatments on the horizon.

Watch this series from the beginning: Defining Hormone-Sensitive Prostate Cancer, and When to Consider PSMA PET Scans

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Dr. Riaz:
I think moving on from radiopharmaceuticals, there are also some newer interesting targets beyond radiopharmaceuticals. What are your thoughts about immunotherapy in prostate cancer?

Dr. Kantala:
It’s making its way up, I haven’t incorporated upfront, but in later lines.

Dr. Ewing:
And certainly we’ve seen really good responses in the appropriate patients that have the appropriate NGS findings.

Dr. Cherington:
Yeah. I feel like the patient population that it might benefit is pretty small right now, but maybe with combination or knowing the best biomarkers and when to use it we’ll have a better sense in the future.

Dr. Riaz:
I think these are great points, and I absolutely agree that at the moment, the patient population where is likely to benefit is really small. The patients who have mismatch repair deficits or high TMB, TMB greater than 10.

I think the more interesting part of immunotherapy is moving beyond these PD-1 and PD-L1 inhibitors. It’s really these bispecific T-cell engagers or these bispecific antibodies, which can target immune system in a different way. Are you running any active trials in this space or have you seen any patient getting treatment with these newer T-cell engagers?

Dr. Cherington:
No, we’re not right now.

Dr. Kantala:
Not yet.

Dr. Cherington:
It’ll be interesting to see what the survival data is when it comes out or the potential benefits of it. And then also how does it compare to other BiTE therapies and other cancer groups as far as the CRS and different toxicities and chronic immune suppression.

Dr. Riaz:
Yeah. I mean these great points. I think there’s early data from T-cell engagers in the context of different tumor-specific antigens. Regardless of whether you think about STEAP1, DL3, I think the benefit we’re seeing is modest. But I think that’s partly also the fact that we are using these drugs so late in the prostate cancer course where they’ve already used most of taxanes, ARPIs, maybe if they’re used somewhat earlier in the prostate cancer state, we may be seeing better results.

I think there’s also interesting targets with AR degraders in this space. So truly I think exciting time for our patients even with castration-resistant disease, which is really considered a bad prognostic sign for these patients.

I just want to close the discussion by getting your overall thoughts on management of CRPC. How do you suggest we think about sequencing and any takeaways from the management of castration-resistant prostate cancer in the metastatic state?

Dr. Cherington:
I mean, from my standpoint, I just want to put a plug in for lifestyle medicine, exercise, nutrition, and just the importance of that for every cancer type, but particularly with prostate cancer. We have a lot of studies just simply walking 30 minutes a day shows better response rates and slower growth of prostate cancer. So bringing in that lifestyle is always very important.

But then also just looking at all your options, molecular studies, comorbidities, trying to give the patient a good realistic view of what to expect and what are the potentials that we can offer so that they can have a good shared decision making.

Dr. Kantala:
Yeah. I think apart from those very rare transformers where there’s a very aggressive transformation, most patients… I’ve been practicing more than a decade and decade and a half, we had options. We have more options. It’s even though it’s castration-resistance, widespread disease, there’s still options and multiple lines of therapies.

Definitely very exciting times we are in, and I’m sure it’s going to be only getting better from here. I’m very happy for my patients with available… As I said, our armory is still getting filled with more and more options in it.

Dr. Ewing:
I think it’s an exciting time to be in GU Oncology because we’ve got so many new treatment options coming. The era of single agent ADT, I think is largely gone for most patients, although there’s a subgroup where that’s still very relevant and I think it’s exciting to have just an ever-enlarging armatorium to approach each patient with individualized care.

Dr. Riaz:
Yeah, I think this is fantastic. I think the key takeaway is some discussions seem to be that the multiple life-prolonging agents, we should make sure that patient receive as many life-prolonging agents as possible.

I think then there are tools that can help us decide sequencing, although there’s no perfect sequence, but the tools which can help us strategize which treatment to come first and which to come later, make sure that we’re still using the bone-strengthening agents in CRPC state with bone metastases.

And finally, I think we need to think about clinical trials so that we can keep bringing new treatment options for our patients.