Olaparib for Metastatic Castration-Resistant Prostate Cancer
Open accessAbstract
BACKGROUND: Multiple loss-of-function alterations in genes that are involved in DNA repair, including homologous recombination repair, are associated with response to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition in patients with prostate and other cancers. METHODS: ; cohort B (142 patients) had alterations in any of 12 other prespecified genes, prospectively and centrally determined from tumor tissue. Patients were randomly assigned (in a 2:1 ratio) to receive olaparib or the physician's choice of enzalutamide or abiraterone (control). The primary end point was imaging-based progression-free survival in cohort A according to blinded independent central review. RESULTS: In cohort A, imaging-based progression-free survival was significantly longer in the olaparib group than in the control group (median, 7.4 months vs. 3.6 months; hazard ratio for progression or death, 0.34; 95% confidence interval, 0.25 to 0.47; P<0.001); a significant benefit was also observed with respect to the confirmed objective response rate and the time to pain progression. The median overall survival in cohort A was 18.5 months in the olaparib group and 15.1 months in the control group; 81% of the patients in the control group who had progression crossed over to receive olaparib. A significant benefit for olaparib was also seen for imaging-based progression-free survival in the overall population (cohorts A and B). Anemia and nausea were the main toxic effects in patients who received olaparib. CONCLUSIONS: In men with metastatic castration-resistant prostate cancer who had disease progression while receiving enzalutamide or abiraterone and who had alterations in genes with a role in homologous recombination repair, olaparib was associated with longer progression-free survival and better measures of response and patient-reported end points than either enzalutamide or abiraterone. (Funded by AstraZeneca and Merck Sharp & Dohme; PROfound ClinicalTrials.gov number, NCT02987543.).
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In PCa, olaparib is effective in patients with mutations in DNA repair genes.
“In PCa, olaparib has gained attention for its effectiveness in patients with mutations in DNA repair genes, offering a targeted treatment approach [28, 30].”
From Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer (2024) · cites this paper as [28]
The Discussion reports significantly longer imaging-based progression-free survival with olaparib than with control treatment in patients with BRCA1, BRCA2, or ATM alterations. The Methods limit the trial to men with metastatic castration-resistant prostate cancer whose disease had progressed on a new hormonal agent; the claim's broader reference to prostate cancer does not preserve that qualification. (LLM, conf=0.84)
Experimental — accuracy not yet measuredOlaparib has been approved for treating metastatic breast cancer and mCRPC patients harboring genetic mutations in HRR genes.
“Olaparib, a PARP inhibitor, has garnered approval for treating metastatic breast cancer and mCRPC patients harboring genetic mutations in HRR genes [28, 39].”
From Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer (2024) · cites this paper as [28]
The Methods and results describe olaparib treatment and benefit in men with mCRPC and alterations in homologous-recombination-repair genes. The References list an olaparib study in metastatic breast cancer. Neither passage establishes that olaparib had regulatory approval for either indication. (LLM, conf=0.85)
Experimental — accuracy not yet measuredOlaparib has shown substantial efficacy in various cancers, including ovarian, breast, and PCa.
“Olaparib, has shown substantial efficacy in various cancers, including ovarian, breast, and PCa [26–28].”
From Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer (2024) · cites this paper as [28]
The Results report substantially longer imaging-based progression-free survival with olaparib in men with metastatic castration-resistant prostate cancer and specified DNA-repair gene alterations. The paper cites olaparib studies in breast and ovarian cancer, but the passages in our copy do not report efficacy findings for those cancers, so that part of the claim is not established by this source. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn the phase 3 randomized trials PROfound and TRITON-3, treatment with PARP inhibitors was favored in both chemotherapy-naïve patients and those who had received prior taxane-based chemotherapy.
“In the phase 3 randomized trials PROfound (NCT02987543), and TRITON-3 (NCT02975934), treatment with PARP inhibitors was favored in both chemotherapy-naïve patients and those who had received prior taxane-based chemotherapy [57, 58].”
From Navigating therapeutic sequencing in the metastatic castration-resistant prostate cancer patient journey (2025) · cites this paper as [58]
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“In PCa, olaparib has gained attention for its effectiveness in patients with mutations in DNA repair genes, offering a targeted treatment approach [28, 30].”
Background
- Authors
- de Bono, J., Mateo, J., Fizazi, K., Saad, F., Shore, N., Sandhu, S., Chi, K. N., Sartor, O., Agarwal, N., Olmos, D., Thiery-Vuillemin, A., Twardowski, P., Mehra, N., Goessl, C., Kang, J., Burgents, J., Wu, W., Kohlmann, A., Adelman, C. A., & Hussain, M.
- Affiliations
- From the Institute of Cancer Research and Royal Marsden Hospital, London (J. de Bono), and AstraZeneca, Translational Medicine, Cambridge (C.A.A.) — all in the United Kingdom; Vall d’Hebron Institute of Oncology and Vall d’Hebron University Hospital, Barcelona (J.M.), the Spanish National Cancer Research Center, Madrid (D.O.), and Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, Malaga (D.O.) — all in Spain; Institut Gustave Roussy, University of Paris Sud, Villejuif (K.F.), and...
- Université Paris-Sud (FR)
- Institut Gustave Roussy (FR)
- Peter MacCallum Cancer Centre (AU)
- BC Cancer Agency (CA)
- Tulane University (US)
- Huntsman Cancer Institute (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- AstraZeneca (United Kingdom) (GB)
- Northwestern University (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-05-28
- Volume
- 382
- Issue
- 22
- Pages
- 2091-2102
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3020771563
- Cited by
- 2,323
- References
- 32
- Citations by year
- 2026: 264 · 2025: 342 · 2024: 382 · 2023: 396 · 2022: 414 · 2021: 394 · 2020: 125 · 2014: 1
- FWCI
- 120.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- AstraZeneca (N/A)
- Merck Sharp & Dohme (N/A)
- Topics
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
- Keywords
- olaparib, metastatic castration-resistant prostate cancer, PARP inhibition, homologous recombination repair, enzalutamide, abiraterone, progression-free survival, overall survival, anemia, nausea
- MeSH terms
- Poly(ADP-ribose) Polymerase Inhibitors, Loss of Function Mutation, Progression-Free Survival, Aged, Aged, 80 and over, Androstenes, Antineoplastic Agents, Benzamides, Humans, Male, Middle Aged, Neoplasm Metastasis, Nitriles, Phenylthiohydantoin, Phthalazines, Piperazines, Genes, BRCA1, Genes, BRCA2, Ataxia Telangiectasia Mutated Proteins, Prostatic Neoplasms, Castration-Resistant
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