Centering discussion on a patient case of high-volume metastatic CSPC, expert panelists review the option of triplet therapy based on the PEACE-1 trial.
Bobby Liaw, MD: It is my pleasure to present our second case. This is a 59-year-old man who initially presents to the emergency room with severe pain in his right thigh. Further work-up in the emergency room shows that he has an unprovoked fracture in his right thigh. Additional labs are drawn and through the course of the work-up it is notable that his PSA [prostate-specific antigen] levels are quite elevated at 500 ng/mL. Notably, his hemoglobin is 9.8 [g/dL] with ANC [absolute neutrophil count] of 1.7. He ended up undergoing a prostate biopsy that showed Gleason score of 8, 4+4 disease. Bone scan shows 8 foci of bone metastasis, including the femur and vertebrae, and CT of the abdomen and pelvis is notable for peritoneal lymphadenopathy. This is otherwise a 59-year-old man with no medical comorbidities. Prior to the unprovoked pathologic fracture, he had ECOG [Eastern Cooperative Oncology Group] performance status of 0. This patient in summary has a diagnosis of de novo high-volume metastatic castration-sensitive prostate cancer metastatic castration-sensitive prostate cancer. He is eventually started on triplet therapy with ADT [androgen deprivation therapy], docetaxel, and abiraterone.
Neeraj Agarwal, MD: Thank you, Bob, for presenting this case with high-volume de novo [mCSPC]. What made you choose triplet therapy with ADT plus abiraterone plus docetaxel?
Bobby Liaw, MD: In a case like this, we have a lot of the same options that we have spoken about before in terms of doublet therapy. A couple of things to highlight: This is a guy who comes in with de novo disease, which typically has worse prognosis as compared with when metastatic recurrence comes back on metachronous end. We want to put our best foot forward so to speak. He is a 59-year-old guy, otherwise independent, no medical issues, and highly symptomatic. He has had a pathologic fracture, and he would be at risk for other catastrophic problems if any of this disease were to progress. We are given his PSA numbers, which are tremendously elevated. Everything leads for not just high-volume disease but there are many aspects of this disease that are high risk as well. In thinking about data that support use of triplet regimen like ADT, docetaxel, abiraterone, triplet combination was really championed by the PEACE-1 study and in the backdrop of understanding that adding a layer of intensification with doublet combination therapy has seen a success across all the different agents for metastatic hormone-sensitive prostate cancer, this study looked to push that envelop a bit further by adding a third agent. We know that prostate cancer has some intrinsically heterogeneity property. There are going to be some early clones that are more inherently insensitive or resistant to ADT or maybe AR androgen receptor-directed therapy through mechanism such as AR variants or alterations. Trying to have something in the chemotherapy category as well as AR-directed category, it was hoped that they would show that triplet regimen would elevate survival on top of just ADT plus docetaxel alone….PEACE-1 has an interesting study design because it evolved as standard of care evolved. It was initially designed as a large forearm randomized study designed to test whether the addition of abiraterone, radiation therapy, or the combination of both to standard of care at the time, which was ADT, would benefit men with hormone-sensitive prostate cancer. However, that’s what standard of care was at the time and as data from CHAARTED and STAMPEDE came out showing the additional benefits of docetaxel; the study was later amended to allow the addition of docetaxel to be included as standard of care. I would also mention along with that amendment, it also laid out a prespecified statistical plan that provides for primary efficacy analysis of survival with the addition of abiraterone to the docetaxel-treated population. This study was very positive, but more to our point of the triplet regimen focusing on the population of patients who got both ADT and docetaxel as part of standard of care. The addition of abiraterone demonstrated significant improvement in overall survival with hazard ratio of 0.75. If we dug a bit deeper, we saw this positive effect on overall survival was primarily pronounced in the patients with high-volume disease with an adjusted hazard ratio of 0.72. It’s really for these men, the high-volume patients, that we wanted to make sure that if they are already decided for combination chemotherapy, hormonal therapy, that the addition of abiraterone here is of serious consideration because there is survival benefit linked here.
Neeraj Agarwal, MD: Before we go to the low volume, thank you so much for summarizing the PEACE-1 data so well, Bobby….PEACE-1 only allowed accrual of de novo patients. These were patients with de novo high-volume metastatic disease…who had the benefit of adding abiraterone to the backbone of ADT plus docetaxel.
Transcript edited for clarity.