Switching to a patient scenario of metastatic hormone-sensitive prostate cancer, experts discuss which therapeutic approach they would undertake.
Robert Dreicer, MD, MS, MACP, FASCO: We’re going to start talking about the context of metastatic castrate-sensitive prostate cancer. Let me present a case here. This is a 70-year-old gentleman, who’s 4 years out from a robotic prostatectomy Gleason 4+3, grade group 3. He disappeared for a couple of years, went on a bicycle trip to China. He now presents with intermittent right hip pain. His PSA [prostate-specific antigen] is around 50. He’s anemic. His chemistries are OK. He gets a bone scan. He has 2 obvious bone metastasis, 1 in the right femur and 1 in the pelvis. He’s got pelvic nodes that are a bit chunky on CT scans and his performance status is 1. Again, this is a patient who has evolved to metastatic disease. He is not a de novo presentation and he is symptomatic at this juncture. Good performance status. This is not a particularly unique situation. We see patients that do this all the time. We’re going talk briefly about the trials that we’ve done. It’s been a decade since the original charted trial and then the STAMPEDE [Systemic Therapy in Advancing Metastatic Prostate Cancer: Evolution of Drug Efficacy] first presentation. Docetaxel intensification followed by latitude and another STAMPEDE arm leading to the same data with abiraterone [Zytiga] and then a myriad of studies leading to the regulatory approval of both enzalutamide [Xtandi], apalutamide [Erleada]. As we know, we’ll talk a bit about the most recent ARASENS [ODM-201 in Addition to Standard ADT and Docetaxel in Metastatic Castration Sensitive Prostate Cancer] study looking at darolutamide [Nubeqa]. We have this environment where intensification, ADT [androgen deprivation therapy] is a backbone intensification, which may or may not include the addition of radiation therapy. If you have a prostate in place for a de novo presentation, but this patient doesn’t. We know that data. We also know that other than the comparison, which is sort of indirect within STAMPEDE looking at abiraterone and docetaxel because mechanistically they could do that, it looked similar. There is no comparative data. We all see patients. We often make choices about how to approach this patient. I’m going to start with you, Dr George. This patient is sitting in your office. He is as described, and you are now going to start the process. You’ve talked about testosterone suppression, all the things you need to do in terms of trying to deal with the morbidities and comorbidities. You’ve done all that. He has that. What do you tell him in terms of what the natural history is going to be? Do you have the conversation about intensification at that visit? Do you defer it? Give me a bit of what you’re doing with this patient when you see him.
Saby George, MD, FACP: I would be a bit more aggressive with this patient. He’s 70. He’s presenting 4 years after radical prostatectomy and disease on radiographic images, bone scan showing 2 lesions, 1 in the appendicular skeleton and 1 in the axial skeleton. The patient also has some lymph nodes, meaning at least 4 mets [metastases] and patient has anemia as well. Anemia, it’s from the bone met. If you consider bone marrow as an organ, technically he has got organ dysfunction from this. We consider red cell involvement as a high-risk feature. I can sway him to a high-risk or high-volume category based on the presentation. I would present ADT plus docetaxel and/or one of the newer agents based on the newer data. That’s how I would approach this patient. Given the fact that the patient has probably pain, I’d be very careful how I initiate the ADT. We tend to initiate ADT at the same visit using LHRH [luteinizing hormone-releasing hormone] antagonists like degarelix. That way they can be medically castrated within 3 days, symptoms are relieved and within a week or so, I tend to initiate docetaxel which has been in the practice since 2015 based on ECOG3805 [CHAARTED]. Now, we have data from PEACE-1 and ARASENS trials showing that addition for abiraterone or darolutamide can prolong survival significantly in this category of patients.
Robert Dreicer, MD, MS, MACP, FASCO: Dr George, let me push back on you a bit. PEACE-1 was a completely de novo group of patients, and ARASENS, 86% were de novo. Are you ready to apply both those studies to this patient already? Being a bit provocative here, this isn’t exactly the patient who presented in those 2 trials.
Saby George, MD, FACP: I understand, a de novo patient who presents with metastatic disease at the outset that’s slightly different from a patient who recurred after primary treatment like radiation or radiation or radical prostatectomy. For a practical reason, this patient has symptomatic bone mets [metastasis] and anemia and significant burden of disease.
Robert Dreicer, MD, MS, MACP, FASCO: I’m hearing you say that’s where you’re going. You believe that triplet intensification needs to be applied more broadly, perhaps?
Saby George, MD, FACP: I would push for that in this patient.In an elderly patient, we have to be careful as to what we do to them because some of them are frail also. Adding third triplet therapy may be a bit too much in terms of toxicity and safety management. That has to be considered, and we need to have a long discussion about what does oral mean and if patient is in line with that and performance status is 1 as you mentioned, the patient may be able to get away with it.
Robert Dreicer, MD, MS, MACP, FASCO: Now that you’ve already made your decision, let’s assume regulatory approval of darolutamide in this setting, would you use abiraterone or darolutamide? How are you going to approach making that decision for this patient that you’ve already decided that intensification at that level needs to be done?
Saby George, MD, FACP: That’s a great question. I started thinking about this when these new data came out since ESMO [European Society for Medical Oncology Congress] last year and GU ASCO [American Society of Clinical Oncology Genitourinary Cancers Symposium] this year. Abiraterone may be less safe in this situation. Abiraterone suppressing the adrenal and that has the tendency to increase hypertension more than darolutamide. Abiraterone may be unsafe in this situation compared to darolutamide. Even though there’s no head-to-head data to guide you here, my hunch based on the data is to go with darolutamide.
Transcript edited for clarity.