PARP Inhibitors in Prostate Cancer - Episode 11
Alicia Morgans, MD, MPH, discusses how to select the best treatment for patients with metastatic prostate cancer and the importance of monitoring them while on therapy.
Matthew Fowler: What factors do you consider while trying to determine the most appropriate treatment for a patient?
Alicia Morgans, MD, MPH: Thank you for the question. I failed to elaborate on chemotherapy, which of course is an option in mCRPC [metastatic castration-resistant prostate cancer]. Both docetaxel and cabazitaxel are options. The reason it’s important to mention these among all the other options is because I use a combination of clinical factors associated with the cancer, patient factors associated with the fitness of the person who has cancer, and patient preferences and needs to try to decide which treatment is the best choice for each patient. At present, other than our germline and somatic testing looking for mutations, we don’t have a specific test that tells us which treatment is going to be most effective, last the longest, or have the most impact against the cancer. We have to use our understanding of the cancer, the individual man, and his preferences and beliefs to find that right treatment.
For example, if a patient is very symptomatic and has quickly progressing cancer—it may be in the liver or causing cord compression or extreme complications with significant progression in a short period of time—chemotherapy can be the right treatment at that time in combination with ADT [androgen deprivation therapy]. Because we know that chemotherapy is a cytotoxic agent and can have a big effect in a relatively short period of time. If a patient has relatively slowly progressive disease, no visceral involvement in the liver, relatively slowly rising PSA [prostate-specific antigen], and minimal changes on scans, sipuleucel-T might be the right option and partner for ADT, because that’s a treatment for asymptomatic or relatively asymptomatic individuals. If a patient has bone-only metastatic disease, especially if it’s causing pain, something like radium could be a good partner for ADT.
These are different ways we think about it. Patients also come into play because if a patient would prefer to have an oral agent, avoid losing his hair, or have some separation from the clinic in terms of not needing an infusion, an oral agent like a PARP inhibitor might be best for him if he’s eligible and has a DNA-repair defect mutation that may make him sensitive. It’s all these things taken together and a conversation with an individual patient and whoever else is at the visit—a loved one or caregiver—to make those decisions as a team.
Matthew Fowler: How do you monitor patients once they start whichever therapy that you assign and agreed on with their team? And what are some signs and symptoms of disease progression or recurrence that you’re looking for?
Alicia Morgans, MD, MPH: That’s a great question too. As oncologists, urologists, and others who may take care of these types of patients, we recognize that we need to monitor 2 things. We need to monitor for safety and ensure that the treatment we’re giving isn’t causing complications that could put an individual at risk, and we also need to monitor for disease response or progression. We have to do tests that cover those 2 aspects of a patient’s care.
From a safety perspective, we typically follow CBCs [complete blood counts] to make sure that whatever we’re using for a patient isn’t causing cytopenias, because several of our treatments can absolutely cause cytopenias. With treatments like chemotherapy or PARP inhibitors, these are things we’d want to monitor. We also typically follow complete metabolic panels, which include things like kidney and liver function to ensure that we aren’t causing patients to have derangements in either area, or electrolyte abnormalities that we may need to correct because the patient is becoming dehydrated or whatever the issue is. From a safety perspective, those are things that must be done and monitored closely.
From a disease control perspective, we monitor PSA. We’ll typically collect that when we collect the rest of the laboratory tests, which in my clinic is usually every 3 to 4 weeks, depending on where we are in terms of which treatment we’re using. If we have a patient on an AR [androgen receptor]–targeted agent and they’ve been stable on that agent for 6-plus months, we might do it less commonly, like every 6 weeks or even every 12 weeks, depending on the patient and his individual plan. But for things like chemotherapy, we’re monitoring these things every 3 weeks, and with PARP inhibitors, maybe every 4 weeks. It depends on the treatment and how we’re doing that.
We also often check testosterone, at least intermittently, to make sure we have the patient on an effective backbone of androgen deprivation therapy that’s keeping the testosterone firmly low. We also get scans, which depends on the type of treatment that we’re using to try to care for the patient. Usually these scans are done every 8 to 12 weeks—more frequently if there’s concern based on clinical symptoms, pain, or other reasons that we might need to do them more often.
This transcript has been edited for clarity.