# PROfound

Source: https://onco.cc/trials/profound/  
OnCo record `profound` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first biomarker-selected trial in prostate cancer to improve survival, using a PARP inhibitor in men with BRCA-type mutations.

## Summary

PROfound, trial NCT02987543 sponsored by AstraZeneca and Merck and reported in 2020, was the first biomarker-selected trial in prostate cancer to improve survival, using the PARP inhibitor olaparib in men with BRCA1, BRCA2 or ATM alterations. It randomised 387 men with metastatic castration-resistant prostate cancer and homologous recombination repair alterations after an androgen receptor pathway inhibitor to olaparib or a switch to enzalutamide or abiraterone, met its primary radiographic progression-free survival endpoint in cohort A with a large effect, and showed a survival benefit despite crossover, leading to approval in May 2020. OnCo links it to BRCA1 and BRCA2 and PARP as targets, to Maha Hussain and Johann de Bono. Whether ATM and other non-BRCA alterations truly benefit is the open question the cohort structure left behind.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-06
- Registry id: NCT02987543
- Phase: 3
- Setting: mCRPC with HRR gene alterations after ARPI: olaparib vs enzalutamide/abiraterone switch
- Sponsor: AstraZeneca / Merck
- Enrolled: 387
- Result: rPFS HR 0.34; OS HR 0.69 (cohort A).
- Outcomes: Radiographic progression-free survival, cohort A (BRCA1/2, ATM): Olaparib 7.4 months vs Enzalutamide or abiraterone 3.6 months, HR 0.34; Overall survival, cohort A: Olaparib 19.1 months vs Enzalutamide or abiraterone 14.7 months, HR 0.69
- Replication: Consistent with TRITON3 (rucaparib in BRCA-altered mCRPC).

## Notes

- In England NICE TA887 recommends olaparib within its marketing authorisation for hormone-relapsed metastatic prostate cancer with BRCA1 or BRCA2 mutations that has progressed after a newer hormonal treatment such as abiraterone or enzalutamide, subject to the commercial arrangement. The evaluation updated the cost-effectiveness estimates of TA831 without reviewing new clinical evidence. The committee noted that retreatment with abiraterone or enzalutamide, the comparator in the trial, is not considered effective and is not standard care in the NHS, and that the company provided evidence separately for men who had and had not already had a taxane.

## Sources

- ClinicalTrials.gov NCT02987543: https://clinicaltrials.gov/study/NCT02987543
- NICE TA887: olaparib for previously treated BRCA mutation-positive hormone-relapsed metastatic prostate cancer: https://www.nice.org.uk/guidance/ta887

## Connected records

- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/)
- targets: [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [PARP](https://onco.cc/targets/parp/)
- drugs: [Olaparib](https://onco.cc/drugs/olaparib/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/)
- terms: [Prostate cancer drugs in England: what NICE recommends, and what it refuses](https://onco.cc/terms/prostate-uk-drug-approvals/), [Radiographic progression-free survival (rPFS)](https://onco.cc/terms/radiographic-progression-free-survival/), [Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters](https://onco.cc/terms/prostate-hrr-eligibility/)
- trials: [PROpel](https://onco.cc/trials/propel/), [TRITON3](https://onco.cc/trials/triton3/)
- people: [Johann de Bono](https://onco.cc/people/johann-de-bono/), [Maha Hussain](https://onco.cc/people/maha-hussain/)
- key papers: [PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations](https://onco.cc/key-papers/paper-profound-nejm-2020/)
- roadmaps: [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)

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JSON: https://onco.cc/api/v1/entities/profound.json