Clinical trialPhase 3Prostate cancer

Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial

Lancet Oncol · 2023796 patients

Saad F, Clarke NW, Oya M, Shore N, Procopio G, Guedes JD, et al. Lancet Oncol. 2023. 24:1094-1108

Study type: Clinical trial
Study name: PROpel
Phase: Phase 3
Design: Randomised, double-blind, placebo-controlled trial (126 centres in 17 countries)
Sample size: 796 patients
Source: Lancet Oncol · 2023
Trial registration: NCT03732820

In plain words

In this final report, adding olaparib tablets to abiraterone in men with prostate cancer resistant to hormone therapy (not selected by gene mutation) gave a median survival of 42.1 months vs 34.7 months, but this difference was not statistically conclusive. Anaemia (low red blood cells) was the most common severe side effect.

Key results

42.1 vs 34.7 months

Median overall survival

HR 0.81 (0.67–1.00); p=0.054 (not significant)

16% vs 3%

Grade 3–4 anaemia

40% vs 32%

Serious adverse events

Drugs in this study:Abiraterone (Zytiga)Olaparib (Lynparza)

Dose and schedule cards

Olaparib + abiraterone (PROpel)

First-line mCRPC with a BRCA mutation (FDA label indication; ESMO: abiraterone–olaparib for BRCA alterations without prior ARPI)Cycle length: ContinuousOn the page “Prostate cancer” · With DNA repair gene mutations (HRR/BRCA): PARP inhibitors in mCSPC and mCRPC

First-line mCRPC with a BRCA mutation (FDA label indication; ESMO: abiraterone–olaparib for BRCA alterations without prior ARPI)

Drug	Dose	Route	Schedule
Olaparib	300 mg twice daily	Oral	Daily
Abiraterone acetate	1000 mg once daily	Oral, on an empty stomach	Daily
Prednisone or prednisolone	5 mg twice daily	Oral	Daily
ADT (GnRH agonist or antagonist, or prior orchiectomy)	Per formulation	—	Continuous

Cycle length: Continuous
Duration: Until progression or unacceptable toxicity

Per the FDA label and the trial. Grade 3–4 anaemia occurred in 16%; olaparib dose modifications and monitoring as in the PROfound regimen.

On the page “Prostate cancer” · With DNA repair gene mutations (HRR/BRCA): PARP inhibitors in mCSPC and mCRPC

BRCA-mutated mCRPC, with abiraterone (PROpel)

With abiraterone and prednisone or prednisoloneCycle length: ContinuousOn the page “Olaparib (Lynparza)” · Standard dosing (FDA label)

With abiraterone and prednisone or prednisolone

Drug	Dose	Route	Schedule
Continuous
Olaparib	300 mg	Oral (with or without food)	Twice daily (about every 12 hours)
Abiraterone	1000 mg	Oral	Once daily
Prednisone or prednisolone	5 mg	Oral	Twice daily
GnRH analogue	As per that drug's label	Injection	Continue concurrently (unless bilateral orchiectomy has been done)

Cycle length: Continuous
Duration: Until progression or unacceptable toxicity

On the page “Olaparib (Lynparza)” · Standard dosing (FDA label)

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

1Olaparib + abiraterone

Olaparib 300 mg (2 × 150 mg tablets) orally twice daily + abiraterone acetate 1000 mg orally once daily + prednisone or prednisolone 5 mg orally twice daily, with ADT, until radiographic progression or unacceptable toxicity (399 patients).

2Placebo + abiraterone

Olaparib placebo twice daily + abiraterone acetate 1000 mg once daily + prednisone or prednisolone 5 mg twice daily (397 patients).

Source of the regimen details: ClinicalTrials.gov NCT03732820 and the FDA label for LYNPARZA (DailyMed)

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

796 patients aged 18 or older with first-line mCRPC (no prior systemic treatment for mCRPC; prior abiraterone not allowed; prior docetaxel at the localised or hormone-sensitive stage allowed), continuing ADT with testosterone below 50 ng/dL, ECOG performance status 0 to 1, life expectancy of at least 6 months, not selected by HRR status (HRR status determined after enrolment by tissue and ctDNA testing). Class II–IV heart failure or ejection fraction below 50% and uncontrolled hypertension were exclusion criteria.

Endpoints

Primary outcome: radiographic progression-free survival; alpha-controlled key secondary outcome: overall survival (two-sided alpha threshold at the final analysis 0.0377).

Safety and side effects

The most common grade 3–4 adverse event was anaemia (16% versus 3%). Serious adverse events 40% versus 32%; one treatment-related death (interstitial lung disease) in the placebo group. According to the FDA label: anaemia 48% (grade 3–4: 16%) versus 18% (3.3%); fatigue 38% versus 30%; nausea 30% versus 14%. Olaparib interruption 48%, dose reduction 21% and permanent discontinuation 16%.

Clinical significance and place in guidelines

The overall survival benefit in the overall population was not statistically significant; for this reason, use of the combination has largely been restricted to patients with BRCA gene alterations, and the ESMO 2026 guideline recommends abiraterone–olaparib in patients with BRCA alterations who have not previously received an ARPI.

Limitations

Patients were enrolled without selection by HRRm; BRCA subgroup analyses are not reported in the abstract and are exploratory.

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.