Second-Line Treatment Options in Advanced Prostate Cancer - Episode 1

First-Line Therapy Options in Metastatic Castration-Resistant Prostate Cancer

Robert Dreicer, MD, provides an overview of the first-line therapy options available in metastatic castration-resistant prostate cancer and the recent advances in detection, diagnosis, and treatment.

Robert Dreicer, MD: Metastatic castration-resistant prostate cancer as a sort of a disease state has evolved pretty dramatically over the last couple of years, and we’re really poised to make additional changes. Among the most important issues is actually what happens in the castrate-sensitive metastatic setting. When people talk about a sequence of therapies, the first thing you have to figure out is, what happened when they were castrate-sensitive metastatic? We know that there is level 1 evidence, really practice-changing evidence, that ADT, androgen deprivation therapy, intensification with drugs like abiraterone [Zytiga], or apalutamide [Erleada], or enzalutamide [Xtandi], or docetaxel is the standard of care. We also know that its adoption rate still has a ways to go. When somebody says to me, “What’s a standard sequence for a patient with mCRPC [metastatic castration-resistant prostate cancer]?” There is no standard answer. You have to understand where we were in terms of what the patient’s received, what’s the clinical setting that the patient is currently in, is the patient symptomatic, or is this a PSA [prostate-specific antigen] only mCRPC progression? Are you a user of sipuleucel-T [Provenge] or not? Do you have investigation studies available? Did the patient receive an androgen receptor inhibitor? Abi [abiraterone], or enza [enzalutamide], or apa [apalutamide], in the castrate-sensitive setting? Because that will dictate changes and other changes are coming. We anticipate perhaps early in 2022, FDA [Food and Drug Administration] approval of an agent lutetium-177- PSMA [prostate-specific membrane antigen]-617 adding yet another drug to the mCRPC setting. There’s also evidence that likely will be presented over the next couple of months, which might suggest that patients benefit in the mCRPC setting by adding an ARI [androgen receptor inhibitor], drugs like abiraterone, or perhaps enzalutamide to a PARP inhibitor. There are a lot of changes, and you really have to sort of pay attention, but I think the key is the context of where the patient is by the time they arrive at mCRPC.

When people ask the question, what are frontline therapies for patients with mCRPC? Again, one of the things that I take into consideration before I answer the question is, where is the patient in terms of prior therapies? Were they a de novo presentation with metastatic disease and were they intensified with drugs like docetaxel or an ARI? Were they evolved from prior local therapy to metastatic disease and received androgen deprivation therapy only? What’s the context of where they are in terms of mCRPC? For example, is it a patient who got intensified with abiraterone, and now has a slowly rising PSA in a castrate setting, completely asymptomatic? Versus a patient who again maybe had ADT primarily, and now has not only biochemical progression but has new bone metastases and is symptomatic. How we approach these 2 different patients would be very different. There is limited sequence level 1 evidence to tell us that you must do X, Y, and Z, and part of it is because of not only the heterogeneity of the disease itself but increasingly the kinds of therapies that these patients may have seen prior. And that also may include genomic data. What is the BRCA [BReast CAncer gene] or ATM [ataxia telangiectasia mutated] status of a patient? Are there DDR [DNA-damage response] mutations?There’s no simple answer, but there is a way of thinking about the clinical spectrum that you have to start with to identify what might be the optimal therapy for an individual patient.

Transcript edited for clarity.