# PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations

Source: https://onco.cc/key-papers/paper-profound-nejm-2020/  
OnCo record `paper-profound-nejm-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In men with metastatic castration-resistant prostate cancer carrying BRCA1, BRCA2 or ATM alterations who had progressed on hormonal therapy, the PARP inhibitor olaparib delayed progression and lengthened survival compared with another hormonal agent.

## Summary

Phase 3 trial of 387 men with metastatic castration-resistant prostate cancer progressing on enzalutamide or abiraterone, with alterations in BRCA1, BRCA2 or ATM (cohort A) or 12 other homologous recombination genes (cohort B), randomised 2:1 to olaparib or physician's choice of enzalutamide or abiraterone.

In cohort A median progression-free survival was 7.4 versus 3.6 months (hazard ratio 0.34) and median overall survival 19.1 versus 14.7 months (hazard ratio 0.69 despite crossover); benefit was driven mainly by BRCA2.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2020
- DOI: 10.1056/NEJMoa1911440
- Authors: de Bono J, Mateo J, Fizazi K, et al.
- Findings: Cohort A: median progression-free survival 7.4 vs 3.6 months; hazard ratio 0.34.; Cohort A: median overall survival 19.1 vs 14.7 months; hazard ratio 0.69.
- What it means: Germline and tumour testing for homologous recombination repair genes is now standard in metastatic prostate cancer, and olaparib is approved for BRCA-mutated disease after a hormonal agent.
- Caveats: Benefit in ATM and the cohort B genes was weak or absent.; The comparator, a second hormonal agent, has limited activity after progression on the first.

## Sources

- N Engl J Med 2020: https://doi.org/10.1056/NEJMoa1911440
- PubMed: https://pubmed.ncbi.nlm.nih.gov/32343890/

## Connected records

- roadmaps: [Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch](https://onco.cc/roadmaps/prostate-roadmap/)
- key papers: [TOPARP-A: DNA-repair defects and olaparib in metastatic prostate cancer](https://onco.cc/key-papers/paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015/), [TRITON2: rucaparib in men with metastatic castration-resistant prostate cancer harbouring a BRCA1 or BRCA2 alteration](https://onco.cc/key-papers/paper-abida-triton2-rucaparib-brca-jco-2020/), [TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-fizazi-triton3-rucaparib-nejm-2023/)
- ideas: [Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later](https://onco.cc/ideas/idea-prostate-hrr-testing-at-metastatic-diagnosis/)
- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- targets: [ATM](https://onco.cc/targets/atm/), [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [CDK12](https://onco.cc/targets/cdk12/), [PARP](https://onco.cc/targets/parp/)
- drugs: [Olaparib](https://onco.cc/drugs/olaparib/)
- pathways: [Base excision repair, PARP & alkylation damage](https://onco.cc/pathways/base-excision-repair-parp/), [Double-strand break repair: HR versus end joining](https://onco.cc/pathways/homologous-recombination-repair/), [Synthetic lethality: paired dependencies](https://onco.cc/pathways/synthetic-lethality-map/)
- terms: [Germline BRCA mutation (gBRCA)](https://onco.cc/terms/gbrca-mutation/), [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/)
- trials: [PROfound](https://onco.cc/trials/profound/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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