Treatment Options for Metastatic CRPC


An expert in prostate cancer reviews available options for the treatment of mCRPC and considerations for selecting the optimal therapy.

Scott T. Tagawa, MD, FACP: Fortunately, there are now a number of different options for the treatment of patients with metastatic castration-resistant disease. That being said, as some of the therapies that were first approved for castration-resistant disease have moved to earlier advanced settings, it’s most appropriate to speak about advanced or metastatic prostate cancer in general, as some of these agents are used in both settings. This is important because one of the factors involved with my decision of what to treat a patient sitting in front of me with has to do with what they’ve received before.

That being said, if I’m seeing a patient with metastatic castration-resistant prostate cancer, I’ll generally discuss 6 different categories of therapies that are somewhat overlapping, depending on viewpoint. There’s hormonal therapy, which is generally androgen receptor [AR] pathway therapy. There’s chemotherapy, which for the most part are taxanes, but could be platinum agents. We still have mitoxantrone, the first drug approved, as well as various other agents for different phenotypes. We have bone-targeted therapy, ie, radium-223, with a survival advantage, as well as supportive care agents, like the bone health agents. We have immunotherapy, so sipuleucel-T, which is autologous cellular immunotherapy. We also have pembrolizumab for the MMR [mismatch repair]-MSI [microsatellite instability] subset that’s on label when they don’t have other options.

I generally speak with a patient about targeted therapy. But talking to physicians, these are all targeted in general, so it’s more appropriate to just call them molecularly selected therapies. I mentioned pembrolizumab, but in addition, the biggest subset of patients we have right now are those with DNA repair, and the PARP inhibitors. At least in the single-agent use, we believe that molecular selection is important, although there are emerging data that maybe in combination, those targeted molecularly selective agents may improve outcomes. Then there’s other, which generally speaking for me are clinical trials. Some of our clinical trials are in one of these categories, or combinations of these categories, but there are also others that don’t quite fit into any of those particular categories.

As I’m assessing a patient sitting in front of me, as I mentioned before, I will certainly look at what types of agents have been administered in the past. In terms of prior therapy, that’s the No. 1 key. I will also look at a combination of how they did in terms of response and duration of response, as well as tolerance to these categories. But at least receiving a category is one of the factors that makes the decision for me. Cancer factors are another decision. How aggressive the disease is, how fast it’s growing, and how symptomatic it is will assist in my decision of which agents to use. There’s also location of therapy. I mentioned bone-specific therapy. Someone could have a lot of bone metastasis and some other forms of metastasis and still benefit from a “bone-only” targeting agent, such as radium. But someone without bone metastasis is less likely to benefit. The liver tends to stand out for a lot of us as we’re picking agents.

Then the patient’s factors, such as performance status and comorbidities, will certainly come into play while picking an agent. And then finally, not that it’s the least important, but there are other patient factors. Sometimes there are 2 options that may be equally suitable, and a lot of times for me that’s a “standard option” and a clinical trial, and I’ll offer both and leave it up to the patient or their family to help choose that, or sometimes their other physicians. Other times, I’ll have a clear recommendation that isn’t in line with the patients and what they want, and we’ll look for something that fits their goals.

It’s wonderful that we’ve made such advances. We’re not in the old days where there was ADT [androgen deprivation therapy] and docetaxel and not much else, where we kept repeating docetaxel or using one of the older anti-androgens. That being said, many of the approved agents are overlapping in terms of mechanism of action and resistance patterns. None of these to date in the traditional settings and how they’re used—single agents or in combinations—lead to cure. All of them have their own toxicity profiles. One clear unmet need is when we’ve moved through all of the agents that are appropriate for an individual, and the patient is still alive with a good performance status and needs something else. Heavily pretreated prostate cancer is a clear unmet need.

As I mentioned a little earlier, sometimes individual treatments aren’t in line with a patient’s beliefs or goals. One of the most common is chemotherapy. I might say that it’s time for chemotherapy. There are certain cases where I say, “You really need chemotherapy now because of rapidly progressive disease in the liver and not many other options.” But there are other times where someone has had one of the AR pathway inhibitors, PSA [prostate-specific antigen] is going up, and they have more lesions on scans, but they feel perfectly well. And if you’re asking me out of all the drugs that we have what is the most likely drug to work next, plainly speaking, I’m going to say chemotherapy. But sometimes the patient doesn’t want chemotherapy. There are other options, whether it’s back-to-back AR-targeted agents, which we generally don’t like to use, but occasionally use in that situation, or clinical trials looking for alternative types of therapy to insert prior to chemotherapy, and in the future, potentially head-to-head against chemotherapy. Those are some of our unmet needs.

Transcript Edited for Clarity

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