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Establishing Treatment Goals: What Are Options for Advanced Prostate Cancer Therapy?

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Establishing Treatment Goals: What Are Options for Advanced Prostate Cancer Therapy? from Patient Empowerment Network on Vimeo.

Prostate cancer treatment goals can vary by patient – thus why it’s essential to have different treatment options. Expert Dr. Xin Gao explains the importance of establishing treatment goals and shares an overview of available options. 

Dr. Xin Gao is a Medical Oncologist at Massachusetts General Hospital. Learn more about this expert Dr. Gao.

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Transcript:

Katherine:

Dr. Gao, now that we know what goes into understanding a patient’s disease, I’d like to talk about treatment, starting with treatment goals. How do goals vary by patient, if they vary at all? 

Dr. Gao:

Sure, yeah. I do think they vary, and I think it is important to be clear about what the realistic goals of treatment might be so that the patient can make an informed decision on how the prostate cancer should be treated or managed. 

Some prostate cancers are highly curable, although there isn’t anything that’s 100 percent, right? And others are curable, but we acknowledge that there may still be a significant risk of relapse despite treatment. And maybe that rough percentage, the probability of cure and sort of the potential downsides or side effects of treatment, that’s something that the patient has to weigh in terms of whether they want to proceed with that treatment or not.   

And then, there are cancers, especially with advanced prostate cancers, that are unfortunately not curable, but yet treatments have the ability to significantly prolong somebody’s life, to slow the cancer progression down or even to shrink it, and to improve cancer-associated symptoms and other sources of distress that we talked about earlier.  

And so, with each patient, I think it is important to talk about these treatment goals because it may not be readily clear, is this a curable cancer or not? And it might not be clear how much benefit they might expect with treatment or are we talking about a marginal benefit? And then that way, you know, they can think about it, talk about it with their family, and kind of factor into their overall benefit risk calculation about whether to do something or not. 

Katherine:

Would you provide an overview of current treatment options for advanced disease? 

Dr. Gao:

Sure. So, it’s a big, very open-ended question, I think.  

So, I think you can divide it up into sort of the major treatment modalities, so things like radiation or radiation types of therapies, chemotherapy, hormonal therapies which are the mainstay of prostate cancer treatments, targeted therapies, and immunotherapies.  

Starting with hormonal therapies which are the backbone of prostate cancer treatments, for advanced prostate cancer, androgen deprivation therapy or ADT is often given indefinitely as the typical standard of care treatment and there are various forms of ADT, most commonly in the form of long-lasting injectable medications – leuprolide (Eligard/Lupron Depot), goserelin (Zoladex), sometimes degarelix (Firmagaon)  is used. And then more recently, there was an FDA approval a couple years ago of an oral pill called relugolix (Orgovyx), which is also a form of ADT or androgen deprivation therapy.  

These medications block the body’s ability to make testosterone which is important for prostate cancer survival and spread. In addition, abiraterone is an oral medication that is also considered a hormonal therapy. It blocks the production on androgens or male sex hormones outside of the testes. That includes the adrenal glands and some other tissues such as prostate cancer itself. And abiraterone (Zytiga) is commonly used in advanced prostate cancer management, in addition to androgen deprivation therapy whereas ADT blocks the testes from making testosterone and androgens, abiraterone blocks the production of androgens outside of the testes.  

And then finally, oral anti-androgen medications that block the prostate cancers from being able to detect androgens or male hormones and to block the androgen receptors on prostate cancers from sending cellular signals for growth and survival are also very commonly used.  

There are older anti-androgen medications like bicalutamide (Casodex), flutamide (Eulexin), lutamide, and there are newer ones, stronger versions, called enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa). For most patients who present with advanced prostate cancer, I think this is much easier, ADT along with either abiraterone or one of the newer, stronger anti-androgens, is the standard of care for most advanced prostate cancer patients with metastatic disease.  

And then, sometimes for patients with higher volume or more aggressive cancers even in the group with metastatic disease, we even add on another treatment, usually chemotherapy, something called docetaxel for what we call triple therapy. And then, maybe that’s a segue to chemotherapy, so docetaxel chemotherapy is a common chemotherapy used for prostate cancer, certainly advanced prostate cancers. Cabazitaxel (Jevtana) is also a common chemotherapy in this situation. These two are related drugs in a family of drugs called taxane chemotherapies and basically they kind of block the trafficking of important components within cancer cells and cause the cancer cell death.  

Docetaxel (Taxotere) is the more commonly used one. It’s typically used earlier, before cabazitaxel. And like I said earlier, for certain patients with what we call high volume metastatic prostate cancer, it’s often used in combination with hormonal therapies early on, what we call upfront therapy for six cycles. If a patient doesn’t receive docetaxel up front, docetaxel is commonly used after progression, after the cancer has progressed on ADT and one of the oral hormone medications.  

Cabazitaxel is more commonly used after a patient has previously received or progressed on docetaxel. Both drugs have been evaluated in randomized Phase III clinical trials and have shown to provide efficacy for patients with advanced prostate cancers.  

In addition to these taxane chemotherapies, platinum chemotherapy, such as carboplatin or cisplatin, are sometimes used for advanced prostate cancers as well, especially for certain neuroendocrine or small cell prostate cancers. These are rarer cancers, but they tend to respond better to platinum-based chemotherapies.   

Or for certain what we call aggressive variant prostate cancers, these platinum-based chemotherapies are also used in combination with either one of the taxanes or with another chemotherapy drug called etoposide. In terms of other treatment modalities, I think recently what we call radiotherapeutics or radioligand therapies have gotten a lot of press with the approval of a new medication called lutetium PSMA or 177 lutetium PSMA 617 (Pluvicto). 

The brand name for that in the U.S. is Pluvicto and what this is is a drug that’s a small molecule that binds to PSMA, which is a protein highly expressed in close to 90% of prostate cancer, advanced prostate cancers. And the small molecule will home to the cancer and it’s linked to radioactive lutetium and the lutetium will decay in that area and lead to cancer cell death.  

So, Pluvicto or lutetium was FDA approved in spring of 2022 based on randomized Phase III trials that show significant efficacy for patients with metastatic castration-resistant prostate cancer who have previously received a second-generation androgen receptor pathway inhibitor, such as abiraterone and enzalutamide, as well as a taxane chemotherapy, like docetaxel or cabazitaxel.  

The medication is given intravenously, once every six weeks, for up to six doses, and there are ongoing clinical trials, actually, that are trying to evaluate this medication in earlier settings where patients haven’t gotten prior chemotherapy before. There was a press release from about half a year ago stating that they’re seeing some early encouraging signs of efficacy with this drug, even in patients who had never received chemotherapy before, so it may be a medication that is going to be used more and more so in more patients even earlier in their course of disease. they’ve shown pretty solid activity for those kinds of cancers. 

What Are Current Prostate Cancer Treatment Options?

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What Are Current Prostate Cancer Treatment Options? from Patient Empowerment Network on Vimeo.

What treatment options are available for prostate cancer patients? Expert Dr. Channing Paller shares an overview of prostate cancer treatment options including surgery, radiation, combination therapies, hormonal therapies, and the PEACE-1 clinical trial.

Dr. Channing Paller is Director of Prostate Cancer Clinical Research at Johns Hopkins Medicine. Learn more about Dr. Paller.

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Transcript:

Katherine:

What are other options that are available now, for patients? 

Dr. Paller:

For curative intent, the main two treatment options are surgery, radiation. Many people for very localized disease are trying other therapies, such as cryotherapy, and more focal therapies. But really, for curative, the standard is surgery or radiation. And as it gets more advanced, circling back to advanced prostate cancer, we are learning that combination therapy is better. So, adding pills like abiraterone, adding systemic therapies, help patients do better. 

So, there’s a big, long list of therapies upfront that we use for metastatic hormone-sensitive prostate cancer. There’s abiraterone, there is apalutamide (Erleada), there’s enzalutamide, and now, darolutamide (Nubeqa).  

And in fact, in fit patients that can tolerate chemotherapy for metastatic high-volume prostate cancer patients, we always recommend triple therapy, either with abiraterone, docetaxel, and ADT, or with darolutamide, docetaxel, and ADT, and these patients really seem to do better for longer. The other thing I would add is the PEACE-1 trial, which looked at abiraterone and docetaxel, found that patients would do best by adding growth factor support. And so, that is recommended. 

The other thing I want to point out to patients is, I know we’re all eager to get started when we find out we have a diagnosis of metastatic prostate cancer, but sometimes, these therapies are quite tough on the system when you have a lot of cancer in your body, and my recommendation to everybody is, one thing at a time. 

So, start the hormone therapy and wait at least 30 days, and in fact, in the PEACE-1 trial, they waited 45 days, right? That allows the testosterone levels to fall, it allows you to adjust to the side effects of hormone deprivation therapy, and it allows your body to be ready for the next line of therapy. And you can add the ADT to second line, such as abiraterone or daro during that time, but not adding the chemo all at once, that really makes a difference. 

I find, unfortunately, when patients and their providers don’t follow those strict criteria, as they did in the trial, meaning they start chemo and abiraterone and ADT on day one, the levels of chemotherapy get higher in the bloodstream because testosterone regulates that, and we’ve published on that before. And they end up with terrible side effects from the chemotherapy, such as neutropenic fever, which means you end up in the hospital with a bloodstream infection and a fever, and more neuropathy, meaning numbness and tingling in your hands and feet. 

And so, I really caution people to spread those therapies out over the first 90 days, and you’ll do better in terms of side effects, and just as well in terms of overall survival. 

Katherine:

Where does hormonal therapy fit into the treatment options, and have there been any advances in hormonal therapy? 

Dr. Paller:

Yes. So, hormonal therapy is the mainstay of how we take care of prostate cancer patients, whether we do this with surgical castration, which is not done very often anymore, or we do it with an LHRH agonist, or we do it with an LHRH antagonist. So, that means that we can do it with medicines that block the signaling, but that tells your body to produce testosterone in various ways. What’s really neat is we’ve made advances, that there are now oral options for some of these therapies. 

In particular, there’s a new therapy called Orgovyx, or relugolix, that is an oral LHRH antagonist that locks testosterone and allows us to stop prostate cancer growth. In addition, there are a variety of LHRH agonists that can be given as subcutaneous shots. 

Treatment Options for Advanced Prostate Cancer

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Treatment Options for Advanced Prostate Cancer from Patient Empowerment Network on Vimeo.

What are treatment options for advanced prostate cancer? Expert Dr. Maha Hussain provides a breakdown of hormone therapy and explains how targeted therapy is used in prostate cancer care.

Dr. Maha Hussain is the Deputy Director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about this expert here.

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Transcript:

Katherine:

Now that we understand how test results can help inform a patient’s cancer and how it may behave. Let’s discuss how they can affect treatment options for men with advanced disease. First, let’s do a brief review of the treatment types currently available. There’s hormone therapy, right. What else?

Dr. Hussain:

Perhaps, it’s simpler if we focus on advanced disease, specifically metastatic disease.

So, if that’s the deal, then the backbone of treatment is hormone treatment. And it really is. We call it hormone, but technically it’s an anti-hormone. What we’re trying to do is shut down the hormonal pathway that stimulate the testes, which is the factory that makes testosterone. So, we are looking at shutting down testosterone production from the testes in order to starve the cancer.

Now, the male hormone is produced predominantly – somewhere about 95 percent of it is made by the testes, and then there are about 5 percent-ish that comes from other sources. These are, again, male hormones like the adrenal gland and so on. And there was a while ago some research – I want to say from the MD Anderson crowd, but this is two years ago – that suggested also that the tumor may start to make sort of in-house production of male hormone to support itself.

Now, having said that, again, testes continue to be the source of the majority of the male hormone. And so, historically, the first data that showed benefit was actually by surgically removing the testes, which is what we call orchiectomy or bilateral orchiectomy. And then medications began hitting the market and were evaluated in the late ’80s and then 1990s, beginning with Lupron – which by the way, in the ’80s, it was an injection that the patient had to give themselves every day, which is remarkable.

But even then, there is a personal preference by patients to go and take injections as opposed to go through surgery with orchiectomy. But still, I would say for some patients it may be an option until it ought to be discussed as an option. Then what we know is this, is because of the potential other sources for the male hormone, the concept of what we call combined androgen depravation was being evaluated.

And again, this goes back to the ’80s when the first drug was flutamide and then bicalutamide, and there are other drugs that became. And they kind of added a sprinkle, I call it, to survival. But it wasn’t dramatic, huge differences in survival. And so, generally, while we used it, everybody believed in using it. Moving forward, the drugs like abiraterone, enzalutamide, apalutamide are the three hormonal drugs that have demonstrated conclusively really an advantage in terms of prolonging life when added to the Lupron.

So, what I tell my patients is that, when it comes to hormone treatment there is really no way around it. You can delay it. Some people are exploring for some patients who don’t have a lot of cancer, maybe a couple of areas, maybe just do targeted radiation and then leave the person alone to buy them some treatment-free time.

And, to me, this is where the discussion that has to happen with the patient. What is the objective? Is the objective to kind of be ahead of the game and maximally treat the cancer with the hope of prolonging life? Or is the objective to delay treatment? And I would tell you that, with these types of conversation, nine out of 10 or 9.5 out of 10 men opt for moving aggressively up front with management. So, that’s that.

Now, the one thing I should point out, one of the trials that also was a landmark trial in this disease was the study CHAARTED, which was an intergroup clinical trial at the time it was designed, led by ECOG, and the PI was Dr. Chris Sweeney. I was part of the team that worked on the design also of the study.

And that was a trial that looked at adding docetaxel to hormone therapy, versus hormone therapy alone, to try to see if it adds something. Historically, all the chemotherapies prior to that that were added to hormone treatment for patients with newly diagnosed metastatic disease had not delivered. And docetaxel did.

However, one thing I should point out, based on that trial – and I don’t want to go into too much details for the sake of time – the patients that seemed to be benefiting were the patients that had more aggressive, more disease in their system. And so, liver metastases, lung metastases spread in the bone at different areas, not like few isolated areas in the spine or the pelvis, but much more than that.

And so, for the patients who have what we call high-volume prostate cancer based on scans – and I’m happy to explain what that means if it’s needed – these are the patients that I would offer either the docetaxel plus hormone treatment, which is the injection, or the injection plus the hormonal pills that I mentioned earlier.

Katherine:

What about targeted therapy? How is that used?

Dr. Hussain:

Okay. So, let’s begin with the molecularly targeted therapy. So, as we speak right now, for patients who have newly diagnosed metastatic disease that we call hormone-sensitive, molecularly targeted therapy is not standard of care. So, I would encourage patients who may qualify for clinical trial to be involved in those. The flipside is – we can talk about it – is that molecularly targeted therapies, specifically with PARP inhibitors have pretty much entered in the space of prostate cancer with a couple of drugs that were FDA-approved.

The other way of targeted treatment, which would be what we refer to targeted radiation, this would be a different story. This is not systemic treatment. This is a local treatment. And what is done is basically if patients do not have a lot of cancer in their body based on scans, and only certain areas, and they are starting systemic therapy, they can certainly consult with a radiation oncologist to target radiation to areas that are visible on scan. So, if somebody has a couple of, let’s say, pelvic bone lesions, maybe a lymph node, and they are already starting systemic therapy, they can consult with a radiation oncologist focal radiation. And so, that would be the general scheme.