Clinical trialPhase 3Prostate cancer

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

Lancet · 20221173 patients (1172 in the analysis)

Fizazi K, Foulon S, Carles J, Roubaud G, McDermott R, Fléchon A, et al. Lancet. 2022. 399:1695-1707

Study type: Clinical trial
Study name: PEACE-1
Phase: Phase 3
Design: Open-label, multicentre randomised trial with a 2×2 factorial design (77 hospitals in 7 European countries)
Sample size: 1173 patients (1172 in the analysis)
Source: Lancet · 2022
Trial registration: NCT01957436

In plain words

In men whose prostate cancer had already spread when it was first found, adding abiraterone tablets (with prednisone) to hormone therapy and chemotherapy delayed the progression of the disease and helped patients live longer. The main extra side effect was high blood pressure, which needs to be monitored.

Key results

HR 0.54

Radiographic progression-free survival — overall population

99.9% CI: 0.41 to 0.71; p<0.0001

HR 0.82

Overall survival — overall population

95.1% CI: 0.69 to 0.98; p=0.030

HR 0.50

Radiographic progression-free survival — ADT + docetaxel population

99.9% CI: 0.34 to 0.71; p<0.0001

HR 0.75

Overall survival — ADT + docetaxel population

95.1% CI: 0.59 to 0.95; p=0.017

Drugs in this study:Abiraterone (Zytiga)Docetaxel (Taxotere)

Dose and schedule cards

Triplet therapy: ADT + docetaxel + abiraterone (PEACE-1)

De novo mHSPC (especially high-volume) in patients suitable for docetaxel; ECOG 0 to 1 (or 2 because of bone pain)Each drug’s schedule in the tableOn the page “Prostate cancer” · Metastatic hormone-sensitive disease (mHSPC)

De novo mHSPC (especially high-volume) in patients suitable for docetaxel; ECOG 0 to 1 (or 2 because of bone pain)

Drug	Dose	Route	Schedule
Docetaxel	75 mg/m²	IV	Day 1 every 3 weeks, 6 cycles
Abiraterone acetate	1000 mg once daily	Oral, on an empty stomach	Daily
Prednisone	5 mg twice daily	Oral	Daily
ADT (GnRH agonist or antagonist, or prior orchiectomy)	Per formulation	—	Continuous

Cycle schedule: Abiraterone and prednisone daily and continuously; docetaxel every 3 weeks (6 cycles); ADT continuous
Duration: 6 cycles of docetaxel; abiraterone + prednisone until progression

Doses from the PEACE-1 trial and its ClinicalTrials.gov registration; in PEACE-1 there was an interval of at least 6 weeks between the start of ADT and the start of docetaxel. Adding abiraterone mainly increased hypertension (grade 3 or higher 22% vs 13%) and did not increase neutropenia or neuropathy.

On the page “Prostate cancer” · Metastatic hormone-sensitive disease (mHSPC)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Standard of care (296 men)

ADT alone or with IV docetaxel 75 mg/m² every 3 weeks.

2Standard of care + radiotherapy (293 men)

Standard of care plus prostate radiotherapy 74 Gy in 37 fractions (3D-CRT or IMRT).

3Standard of care + abiraterone (292 men)

Standard of care plus oral abiraterone 1000 mg once daily with oral prednisone 5 mg twice daily.

4Standard of care + radiotherapy + abiraterone (291 men)

Combination of both interventions: abiraterone 1000 mg once daily + prednisone 5 mg twice daily and prostate radiotherapy 74 Gy in 37 fractions.

Source of the regimen details: ClinicalTrials.gov NCT01957436 (ADT: LHRH agonist/antagonist or orchiectomy; docetaxel 6 cycles of 75 mg/m² every 3 weeks; abiraterone 1000 mg daily + prednisone 5 mg twice daily; radiotherapy 74 Gy in 37 fractions) and abstract of the paper

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Men aged 18 to 80 with de novo metastatic prostate adenocarcinoma (metastases on bone scan, CT or MRI; in node-only disease, only extrapelvic nodes meeting size criteria), ECOG performance status 0 to 1 (or 2 due to bone pain), haemoglobin ≥10 g/dL, neutrophils ≥1500, platelets ≥100 thousand, creatinine less than 1.5 times the upper limit or clearance ≥60 mL/min, potassium ≥4 mmol/L; no more than 3 months of ADT before randomisation.

Endpoints

Co-primary endpoints: radiographic progression-free survival and overall survival; the effect of abiraterone was assessed first in the overall population and then in the population receiving ADT + docetaxel (the population of interest).

Safety and side effects

In the ADT + docetaxel population, grade 3 or higher adverse events occurred in 63% of the abiraterone group and 52% of the group without abiraterone; the largest difference was in hypertension (22% vs 13%). Adding abiraterone did not increase neutropenia, febrile neutropenia, fatigue or neuropathy.

Clinical significance and place in guidelines

PEACE-1, together with ARASENS, established triplet therapy (ADT + docetaxel + ARPI) in de novo mHSPC, especially with high-volume disease, in the EAU and ESMO guidelines.

Limitations

Open-label design; not all patients received docetaxel and the docetaxel population is a subset of the whole trial; standard treatment changed during the enrolment period; data are more limited for low-volume disease.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.