Sequencing Challenges Persist in Metastatic Prostate Cancer

Scott Samuelson, MD

Frontline treatment of patients with metastatic prostate cancer typically includes a taxane-based chemotherapy with docetaxel or an androgen receptor—blocking agent, such as abiraterone acetate (Zytiga). But beyond that, Scott Samuelson, MD, explained that there is no definitive evidence to support the use of one agent over another in subsequent lines of therapy.

However, Samuelson said he encourages providers to talk with their patients about the various costs, comorbidities, and side effects of each treatment.

“One of the good challenges is that we have a lot of options,” said Samuelson, a medical oncologist at Utah Cancer Specialists.

OncLive: What are the biggest challenges in treating patients with metastatic prostate cancer?

What are some challenges that we have with sequencing?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Prostate Cancer, Samuelson discussed frontline treatment of patients with prostate cancer and subsequent sequencing. Samuelson: I have been taking care of patients with prostate cancer for the last 9 years. The management is very different now than it was before because we have so many other options. Figuring out the right way to sequence them is an issue. The costs of the medications, especially the oral medications, is another significant challenge for a significant portion of my patients. There are a lot of opinions on what should be done without any real data to necessarily tell us that one agent is better than another. We certainly know what to do in the first-line metastatic setting for most patients.

What is your preferred frontline therapy, and what factors do you take under consideration when making this decision?

It is not so clear what to do when patients progress on that because we have a number of options. It is a challenge. It is also an opportunity to talk with our patients about the different side effects and costs. Most patients with prostate cancer end up getting most of the available drugs, but we do not know what the proper sequence is at this point. A lot of the decision depends on a patient’s performance status and whether or not they are a candidate for chemotherapy. Considering a patient’s eligibility for chemotherapy is very important, as it is a very effective therapeutic agent. However, abiraterone acetate and enzalutamide (Xtandi) are also great options.

Are there any comorbidities that may affect treatment?

For a lot of patients, the decision comes down to cost. I take care of a number of patients who live several hours from our clinic. For them, an oral agent tends to be preferable. The costs of some of the oral agents, though usually not prohibitive, do pose an additional challenge for some patients. Those are the patients who would prefer an intravenous agent, which tends to be covered better by insurance. Absolutely. Abiraterone is a very well-tolerated drug, but it has significant issues with high blood pressure. That is a common problem I have seen. Enzalutamide is also a wonderful drug, but, compared with abiraterone, it tends to have more fatigue issues. A lot of patients complain about that.

Does olaparib (Lynparza) have a role in treatment for these patients?

What other topics presented at this meeting would you like to highlight?

As more approvals enter the space, what role do you see chemotherapy having?

Does radium-223 dichloride (Xofigo) still have a role in treatment?

With docetaxel, there is certainly preexisting neuropathy; diabetes is fairly common in that population. When I am trying to decide the initial therapy or subsequent therapy, I always look at comorbidities. The addition of olaparib will be great, at least for the 10% to 15% of patients who carry an actionable mutation such as BRCA or ATM. It will be another tool for those patients. PARP inhibitors tend to be well tolerated; I will be excited if that becomes an option. One of the talks centered around nonmetastatic castrate-resistant prostate cancer. In that setting, we have the recent approval of apalutamide (Erleada) as well as enzalutamide. We have all been waiting for an agent to use in that setting. It is very exciting and very helpful, but those drugs have their own set of toxicities. Practitioners need to be careful that they do not immediately jump on those medications without having an extended discussion with their patients about the toxicities. Because we do not yet have an overall survival benefit, toxicity is a big deal. Chemotherapy will continue to have a significant role. Most patients prefer to not have chemotherapy, either from the toxicities that we talk to them about or the experiences family members have had. They tend to prefer oral agents. The oral agents, as a rule, tend to have less toxicity. I do not see a future without chemotherapy, specifically docetaxel, anytime soon because it is such an effective drug. Although it has toxicities, most of them are manageable. Radium-223 definitely has a role, as well, especially in patients who are no longer candidates for chemotherapy or who are not fit enough to get chemotherapy. It certainly has an excellent palliative benefit. It is nice to be able to tell patients that we are still doing something that potentially prolongs their life.