Alan Bryce, MD: Who are the patients where you walk in the room and right off the bat you’re thinking, triplet? “This is aggressive disease, I must think in terms of triplet therapy.” What is that profile?

Benjamin Lowentritt, MD, FACS: That’s typically the de novo patient who is presenting with newly diagnosed prostate cancer, has a PSA [prostate-specific antigen] of likely 50 [ng/mL]-plus, but that doesn’t necessarily disqualify them. They have multiple sites of metastases, and hopefully, and this is where I rely a lot on my medical oncology colleagues, the assessment of being chemotherapy fit. Increasingly that’s becoming the variable more than any other that’s holding back for patients, is it worth adding any of that morbidity consideration of docetaxel? They’re going to get ADT [androgen deprivation therapy], they’re likely going to get on whatever we’re calling the ARPIs [androgen receptor pathway inhibitors], so I think the question then becomes are they qualified for that third therapy? I’m going to push for that patient to get all 3, especially if they’re younger or healthier.

Alan Bryce, MD: I absolutely agree. In the chemotherapy fitness conversation I have with patients we make a couple of points. One is that, we all know that very few patients get to third-, fourth-line therapy, etc, there’s a lot of drop-off, so if you’re going to get the drugs, it’s best to try to get drugs as early as possible, that’s one of the issues. Probably in our practices, since we’re all prostate specialists, we get patients to fourth- or fifth-line therapy, but the real-world data are clear, by the time you get to the third line, you’ve lost 65% of patients. First, second line is as far as you go, and the earlier in the disease process and the fitter you are, the easier it is to get through chemotherapy. An underappreciated point, but the data were clear, came out of the CHAARTED trial, and they showed the quality-of-life data, the patient-reported outcomes for patients who got chemotherapy versus those who got ADT alone. No surprise, what you saw is that during the 4 months of chemotherapy, the patients who got chemotherapy had a slightly lower quality of life, but within 2 months after the end of chemotherapy, those patients had a higher quality of life, and that persisted through the rest of the follow-up period.

It makes the point, and this is a key point I always emphasize to patients and when we think about clinical trials, the primary driver of suffering in a patient with metastatic cancer is uncontrolled cancer. The better disease control we get, the better quality of life the patient has, and we have objective data from clinical trials proving that point. Quality of life is better when we control disease better. I think we’d all say when you have that old, frail patient, that’s not where we’re talking triplet [therapy]. But when we have that 60-year-old man with de novo metastatic prostate cancer, reflecting to the point we were discussing a little earlier, I must justify why not to do triplet. I have to say a triplet is what gives this man the best overall survival, so why am I going to back off from that? I’ve got to have a good reason to accept giving him an inferior overall survival, so what is that reason?

Transcript edited for clarity.