Selecting Between Doublet and Triplet Therapy in Newly Diagnosed mHSPC


Focused discussion on the respective roles of doublet and triplet regimens in patients newly diagnosed with metastatic hormone-sensitive prostate cancer.


Alan H. Bryce, MD: Dr Petrylak, you touched on this a bit earlier, in terms of the clinical factors that you use to stratify patients. Could you talk us through how you think about different types of patients with metastatic hormone-sensitive prostate cancer and who you think of as being more [likely to benefit from] triplet versus doublet therapy?

Daniel P. Petrylak, MD: I’ll talk more about the triplet first and then go on to the doublet. I’m looking for a patient for triplet therapy who is young, firstly who can tolerate treatment, secondly who has aggressive disease as defined by de novo prostate cancer, visceral metastases, liver metastases, more than 4 lesions on a bone scan. Those are generally considered to be high-risk features in this patient. Perhaps the Gleason score would be something else I would include, especially if it’s a Gleason 10. Those are the factors I would use that would lead me to think about using a triple therapy in this patient. If they’re frailer, if I think their prostate cancer is going to be the secondary cause of their demise as opposed to cardiovascular disease, I would do ADT [androgen deprivation therapy] plus another novel agent because I think that’s probably more appropriate. They may not be able to withstand chemotherapy, and there are adverse effects.

The issue is how do you select your next-generation antiandrogen [therapy]? That’s based on adverse effects. Abiraterone does have some known cardiovascular toxicity, as identified by Thomas Jefferson University, showing late cardiac events in these patients with abiraterone. You have to go on chronic steroids with abiraterone, which can cause skin issues. It’s not a high enough dose of steroids to cause diabetes. Liver function abnormalities is another issue. Patients feel fatigued on enzalutamide. They may feel somewhat less fatigued on apalutamide, but that’s at the tradeoff of rash or hypothyroidism. So, there are a lot of pros and cons using the individual antiandrogens.

Alan H. Bryce, MD: Yes, absolutely. Dr Lowentritt, we’ll cycle back with you. Who are the patients for whom, based on the clinical factors, right off the bat, you would say a doublet makes sense? There’s chemotherapy fitness, but is there the chemotherapy-fit patient who nevertheless you’d say a doublet is OK here? As we know in the early days of the CHAARTED and STAMPEDE studies, there was all the conversation around low volume doesn’t need docetaxel, high volume does. Now we’re not even in a monotherapy era anymore for the most part, but in this era are there patients who you feel very comfortable up front saying chemotherapy is probably not necessary?

Benjamin H. Lowentritt, MD, FACS: I appreciate the question because it’s an important distinction in that if you look back from where we are today to a year and a half ago, when we didn’t have the data available on triplet therapy, the vast majority of patients were not getting chemotherapy. It’s not quite right to say that the standard for everyone was chemotherapy. A lot of patients were hopefully not getting monotherapy with ADT, but if they were getting anything they were getting either abiraterone, apalutamide, or enzalutamide predominantly at that point. I think the majority of men we see entering the metastatic space are not necessarily this high volume. They may be older and not necessarily as well functioning. Now we introduce the new imaging options with PSMA PET [prostate-specific membrane antigen positron emission tomography], and we’re identifying patients as metastatic who have lower volume even than what was considered low volume in the CHAARTED and STAMPEDE evaluations from years ago.

There are many patients in there who may be even getting some form of localized therapy, but also getting systemic therapies. I think there are a lot of patients who fall into that group that, yes, you want to give them a therapy that has good survival data, but it probably doesn’t warrant docetaxel, and arguably they may not even benefit from the docetaxel, and certainly may avoid some of those issues that have been discussed about long-term concerns over neuropathy, etc. I think there are a number of patients for whom the sweet spot has been dual therapy with an androgen receptor inhibitor with ADT, and that’s still true today.

Alan H. Bryce, MD: Absolutely.

Transcript edited for clarity.

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