Abiraterone 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.

BACKGROUND

Current standard of care for metastatic castration-sensitive prostate cancer supplements androgen deprivation therapy with either docetaxel, second-generation hormonal therapy, or radiotherapy. We aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care.

METHODS

We conducted an open-label, randomised, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland. Eligible patients were male, aged 18 years or older, with histologically confirmed or cytologically confirmed de novo metastatic prostate adenocarcinoma, and an Eastern Cooperative Oncology Group performance status of 0-1 (or 2 due to bone pain). Participants were randomly assigned (1:1:1:1) to standard of care (androgen deprivation therapy alone or with intravenous docetaxel 75 mg/m

FINDINGS

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 standard of care (n=296), standard of care plus radiotherapy (n=293), standard of care plus abiraterone (n=292), or standard of care plus radiotherapy plus abiraterone (n=291). Median follow-up was 3·5 years (IQR 2·8-4·6) for radiographic progression-free survival and 4·4 years (3·5-5·4) for overall survival. Adjusted Cox regression modelling revealed no interaction between abiraterone and radiotherapy, enabling the pooled analysis of abiraterone efficacy. In the overall population, patients assigned to receive abiraterone (n=583) had longer radiographic progression-free survival (hazard ratio [HR] 0·54, 99·9% CI 0·41-0·71; p<0·0001) and overall survival (0·82, 95·1% CI 0·69-0·98; p=0·030) than patients who did not receive abiraterone (n=589). In the androgen deprivation therapy with docetaxel population (n=355 in both with abiraterone and without abiraterone groups), the HRs were consistent (radiographic progression-free survival 0·50, 99·9% CI 0·34-0·71; p<0·0001; overall survival 0·75, 95·1% CI 0·59-0·95; p=0·017). In the androgen deprivation therapy with docetaxel population, grade 3 or worse adverse events occurred in 217 (63%) of 347 patients who received abiraterone and 181 (52%) of 350 who did not; hypertension had the largest difference in occurrence (76 [22%] patients and 45 [13%], respectively). Addition of abiraterone to androgen deprivation therapy plus docetaxel did not increase the rates of neutropenia, febrile neutropenia, fatigue, or neuropathy compared with androgen deprivation therapy plus docetaxel alone.

INTERPRETATION

Combining androgen deprivation therapy, docetaxel, and abiraterone in de novo metastatic castration-sensitive prostate cancer improved overall survival and radiographic progression-free survival with a modest increase in toxicity, mostly hypertension. This triplet therapy could become a standard of care for these patients.

FUNDING

Janssen-Cilag, Ipsen, Sanofi, and the French Government.

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

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 Myers Squibb, Clovis Oncology, Cougar Biotechnology, Deciphera Pharmaceuticals, Exelixis, F Hoffmann-La Roche, Genentech, GlaxoSmithKline, Incyte Corporation, Janssen-Cilag, Karyopharm Therapeutics, Laboratoires Leurquin Mediolanum, Lilly, Medimmune, Millennium Pharmaceuticals, Nanobiotix, Novartis Farmacéutica, Pfizer, Puma Biotechnology, Sanofi-Aventis, SFJ Pharma, and Teva Pharma; consulting fees from Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Johnson & Johnson, MSD Oncology, Novartis, Pfizer, Roche, and Sanofi; honoraria from Bayer, Johnson & Johnson, and Astellas Pharma; payment for expert testimony from Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Johnson & Johnson, MSD Oncology, Novartis, Pfizer, Roche, and Sanofi; and participation on a Data Safety Monitoring Board or Advisory Board for Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Johnson & Johnson, MSD Oncology, Novartis, Pfizer, Roche, and Sanofi. GR reports honoraria from Astellas Pharma, AstraZeneca, Janssen, Ipsen, and Sanofi; and support for attending meetings from Janssen and Ipsen. RM reports grants from Bayer; honoraria from MSD; and participation on a Data Safety Monitoring Board or Advisory Board for Bristol Myers Squibb, Clovis, Janssen, MSD, and Pfizer. AF reports honoraria from Astellas Pharma, AstraZeneca, Janssen, Novartis, and Sanofi. BT reports grants from Ferring and Bayer; personal fees from Amgen, Astellas Pharma, Ferring, Bayer, Novartis, Myovant, and Sanofi; and non-financial support from Astellas and Janssen. SS reports grants from Astellas Pharma, AstraZeneca, and Janssen; and consulting fees, honoraria, and receipt of equipment from Astellas Pharma, AstraZeneca, Bayer, Ipesen, Janssen, and Takeda. DB reports honoraria from Amgen, Astellas Pharma, Bayer, Janssen, and Novartis. GK reports grants from Astellas Pharma and Janssen; and participation on an Advisory Board and honoraria from Astellas Pharma, AstraZeneca, Janssen, and Sanofi. FC reports honoraria from Bristol Myers Squibb and MSD; and participation on an Advisory Board for AstraZeneca, Bristol Myers Squibb, MSD, Pfizer, and Ipsen. AT-V reports grants from Bayer, Ipsen, and Pfizer; and consulting fees or honoraria from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Ipsen, JNJ, Novartis, MSD, and Roche. BL reports honararia from Janssen; and support for attending meetings from Astellas Pharma, Janssen, and Pfizer. AR reports honoraria from Astellas Pharma, Bayer, and Janssen; and support for attending meetings from Astellas Pharma, Ipsen, and Janssen. NM reports honoraria from Astellas Pharma, Bayer, Ipsen, and MSD. All other authors declare no competing interests.