ArticlesAbiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design
Introduction
After several decades with no substantial progress, the treatment of de novo (synchronous) metastatic prostate cancer has drastically evolved in the past 10 years with the addition of diverse treatments to androgen deprivation therapy (ADT), the former standard of care (SOC). The prognosis for men with de novo metastatic castration-sensitive prostate cancer (mCSPC) has been improved by using ADT concomitantly with either docetaxel1, 2, 3, 4, 5 or one of the second-generation androgen receptor axis inhibitors (abiraterone,6, 7, 8 apalutamide,9 or enzalutamide10, 11). In 2018, radiotherapy to the primary tumour was also shown to extend the overall survival of patients with low-volume metastatic burden.12 The benefits of these various combinatory therapies were confirmed by meta-analyses13, 14, 15 and have helped to shape the current guidelines for the treatment of mCSPC.16, 17, 18
Nevertheless, it remains to be established whether merging some of these new therapies could provide further clinical benefits and, if so, what combination might be most suitable for de novo mCSPC.19 Conducted by a European consortium (PEACE),20 this study aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to SOC (ADT with or without docetaxel).
Section snippets
Study design and participants
We conducted an open-label, randomised, active-controlled, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 sites across seven European countries (Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland). The complete list of inclusion and exclusion criteria is provided in the appendix (pp 5–6). Briefly, male patients aged 18 years or older with histologically confirmed or cytologically confirmed prostate adenocarcinoma documented as de novo metastatic by bone scan, CT, or
Results
Between Nov 27, 2013, and Dec 20, 2018, 1173 patients were enrolled (one patient subsequently withdrew consent for analysis of his data) and assigned to receive SOC (n=296), SOC plus radiotherapy (n=293), SOC plus abiraterone (n=292), or SOC plus radiotherapy plus abiraterone (n=291; figure 1). SOC was ADT alone in 462 patients and ADT with docetaxel in 710 patients (table 1).
For radiographic progression-free survival and overall survival, the median follow-up periods were longer in the overall
Discussion
To our knowledge, this is the first trial to show that a triple systemic therapy, consisting of ADT, docetaxel, and a second-generation androgen signalling inhibitor (abiraterone), extends radiographic progression-free survival and overall survival in patients with de novo mCSPC.
Whether the systemic treatment of high-volume disease (ie, extended metastatic spread) should differ from that of low-volume disease has been extensively debated. The benefit of ADT with docetaxel has been clearly shown
Data sharing
The data collected and analysed for the purpose of the present manuscript are not immediately available due to ethical and legal restrictions. However, Unicancer will grant access to all deidentified individual data underlying the published results upon written and detailed request originating from all personnel involved in cancer research, sent to [email protected].
Declaration of interests
KF reports consulting fees from Amgen, AstraZeneca, Astellas, Bayer, CureVac, Janssen, Novartis, Orion, Pfizer, and Sanofi; honoraria from AstraZeneca, Astellas, Bayer, Janssen, Novartis, and Sanofi; and participation on a Data Safety Monitoring Board for Lilly. JC reports grants from AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, Astellas Pharma, AstraZeneca, Aveo Pharmaceuticals, Bayer, Blueprint Medicines Corporation, BN Immunotherapeutics, Boehringer Ingelheim, Esperia, Bristol
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Members are listed in the appendix (p 2)