Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer
Open accessAbstract
BACKGROUND: We previously reported that olaparib led to significantly longer imaging-based progression-free survival than the physician's choice of enzalutamide or abiraterone among men with metastatic castration-resistant prostate cancer who had qualifying alterations in homologous recombination repair genes and whose disease had progressed during previous treatment with a next-generation hormonal agent. The results of the final analysis of overall survival have not yet been reported. METHODS: , and cohort B included 142 patients with at least one alteration in any of the other 12 prespecified genes. Crossover to olaparib was allowed after imaging-based disease progression for patients who met certain criteria. Overall survival in cohort A, a key secondary end point, was analyzed with the use of an alpha-controlled, stratified log-rank test at a data maturity of approximately 60%. The primary and other key secondary end points were reported previously. RESULTS: The median duration of overall survival in cohort A was 19.1 months with olaparib and 14.7 months with control therapy (hazard ratio for death, 0.69; 95% confidence interval [CI], 0.50 to 0.97; P = 0.02). In cohort B, the median duration of overall survival was 14.1 months with olaparib and 11.5 months with control therapy. In the overall population (cohorts A and B), the corresponding durations were 17.3 months and 14.0 months. Overall, 86 of 131 patients (66%) in the control group crossed over to receive olaparib (56 of 83 patients [67%] in cohort A). A sensitivity analysis that adjusted for crossover to olaparib showed hazard ratios for death of 0.42 (95% CI, 0.19 to 0.91) in cohort A, 0.83 (95% CI, 0.11 to 5.98) in cohort B, and 0.55 (95% CI, 0.29 to 1.06) in the overall population. CONCLUSIONS: and whose disease had progressed during previous treatment with a next-generation hormonal agent, those who were initially assigned to receive olaparib had a significantly longer duration of overall survival than those who were assigned to receive enzalutamide or abiraterone plus prednisone as the control therapy, despite substantial crossover from control therapy to olaparib. (Funded by AstraZeneca and Merck Sharp and Dohme; PROfound ClinicalTrials.gov number, NCT02987543.).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [30]
The Discussion reports longer overall survival with olaparib than with control therapy in men with metastatic castration-resistant prostate cancer whose tumors had BRCA1, BRCA2, or ATM alterations after progression on hormonal treatment. It also says clinical benefit was not observed for patients with other homologous recombination repair gene alterations. The claim is therefore too broad if read as applying to prostate cancer generally or to all DNA-repair gene mutations. Page numbers were not supplied for these passages. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534 · see citing works
Abida, W., Armenia, J., Gopalan, A., Brennan, R., Walsh, M., Barron, D., Danila, D., Rathkopf, D., Morris, M., Slovin, S., et al. (2017) · JCO Precision Oncology · doi:10.1200/po.17.00029 · Cited by 541 · see citing works
Flagged first, then by citations
Research works printed but not linked: 25
- Gillessen S, Attard G, Beer TM, et al. Management of patients with advanced prostate cancer: report of the Advanced Prostate Cancer Consensus Conference 2019. Eur Urol 2020; 77: 508-47.
- Annala M, Vandekerkhove G, Khalaf D, et al. Circulating tumor DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer. Cancer Discov 2018; 8: 444-57.
- Annala M, Struss WJ, Warner EW, et al. Treatment outcomes and tumor loss of heterozygosity in germline DNA repair- deficient prostate cancer. Eur Urol 2017; 72: 34-42.
- Lang SH, Swift SL, White H, Misso K, Kleijnen J, Quek RGW. A systematic re- view of the prevalence of DNA damage response gene mutations in prostate can- cer. Int J Oncol 2019; 55: 597-616.
- Na R, Zheng SL, Han M, et al. Germ- line mutations in ATM and BRCA1/2 dis- tinguish risk for lethal and indolent pros- tate cancer and are associated with early age at death. Eur Urol 2017; 71: 740-7.
- Castro E, Goh C, Olmos D, et al. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival out- comes in prostate cancer. J Clin Oncol 2013; 31: 1748-57.
- Castro E, Goh C, Leongamornlert D, et al. Effect of BRCA mutations on meta- static relapse and cause-specific survival after radical treatment for localised pros- tate cancer. Eur Urol 2015; 68: 186-93.
- Antonarakis ES, Shaukat F, Isaacsson Velho P, et al. Clinical features and thera- peutic outcomes in men with advanced prostate cancer and DNA mismatch repair gene mutations. Eur Urol 2019; 75: 378-82.
- Castro E, Romero-Laorden N, Del Pozo A, et al. PROREPAIR-B: a prospective cohort study of the impact of germline DNA repair mutations on the outcomes of patients with metastatic castration-resis- tant prostate cancer. J Clin Oncol 2019; 37: 490-503.
- Kote-Jarai Z, Leongamornlert D, Saunders E, et al. BRCA2 is a moderate penetrance gene contributing to young- onset prostate cancer: implications for ge- netic testing in prostate cancer patients. Br J Cancer 2011; 105: 1230-4.
- Leongamornlert D, Saunders E, Da- daev T, et al. Frequent germline deleteri- ous mutations in DNA repair genes in fa- milial prostate cancer cases are associated with advanced disease. Br J Cancer 2014; 110: 1663-72.
- Albala DM. Imaging and treatment recommendations in patients with cas- trate-resistant prostate cancer. Rev Urol 2017; 19: 200-2.
- Abida W, Campbell D, Patnaik A, et al. Non-BRCA DNA damage repair gene al- terations and response to the PARP in- hibitor rucaparib in metastatic castration- resistant prostate cancer: analysis from the phase II TRITON2 study. Clin Cancer Res 2020; 26: 2487-96.
- Kaufman B, Shapira-Frommer R, Schmutz ler RK, et al. Olaparib monother- apy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin On- col 2015; 33: 244-50.
- Sandhu SK, Omlin A, Hylands L, et al. Poly (ADP-ribose) polymerase (PARP) in- hibitors for the treatment of advanced germline BRCA2 mutant prostate cancer. Ann Oncol 2013; 24: 1416-8.
- Mateo J, Carreira S, Sandhu S, et al. DNA-repair defects and olaparib in meta- static prostate cancer. N Engl J Med 2015; 373: 1697-708.
- Robson M, Im S-A, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 2017; 377: 523-33.
- Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian can- cer. N Engl J Med 2018; 379: 2495-505.
- Mateo J, Porta N, Bianchini D, et al. Olaparib in patients with metastatic cas- tration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol 2020; 21: 162-74.
- de Bono J, Mateo J, Fizazi K, et al. Olaparib for metastatic castration-resis- tant prostate cancer. N Engl J Med 2020; 382: 2091-102.
- O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Bio- metrics 1979; 35: 549-56.
- Robins JM, Tsiatis AA. Correcting for non-compliance in randomized trials us- ing rank preserving structural failure time models. Commun Stat Theory Meth- ods 1991; 20: 2609-31.
- Khalaf DJ, Annala M, Taavitsainen S, et al. Optimal sequencing of enzaluta- mide and abiraterone acetate plus predni- sone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. Lan- cet Oncol 2019; 20: 1730-9.
- de Bono JS, Chowdhury S, Feyerabend S, et al. Antitumour activity and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer previ- ously treated with abiraterone acetate plus prednisone for ≥24 weeks in Europe. Eur Urol 2018; 74: 37-45.
- de Wit R, de Bono J, Sternberg CN, et al. Cabazitaxel versus abiraterone or enzalu- tamide in metastatic prostate cancer. N Engl J Med 2019; 381: 2506-18.
Cited by
Sorted by citations
Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer
Sartor, O., de Bono, J., Chi, K. N., Fizazi, K., Herrmann, K., Rahbar, K., Tagawa, S. T., Nordquist, L. T., Vaishampayan, N., El-Haddad, G., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2107322 · Cited by 2,864 · see citing works
Self-citationAbiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer
Clarke, N. W., Armstrong, A. J., Thiery-Vuillemin, A., Oya, M., Shore, N., Loredo, E., Procopio, G., de Menezes, J., Girotto, G., Arslan, C., et al. (2022) · NEJM Evidence · doi:10.1056/evidoa2200043 · Cited by 426 · see citing works
Self-citationMorris, M. J., Castellano, D., Herrmann, K., de Bono, J. S., Shore, N. D., Chi, K. N., Crosby, M., Piulats, J. M., Fléchon, A., Wei, X. X., et al. (2024) · The Lancet · doi:10.1016/s0140-6736(24)01653-2 · Cited by 362 · see citing works
Self-citationGillessen, S., Armstrong, A., Attard, G., Beer, T. M., Beltran, H., Bjartell, A., Bossi, A., Briganti, A., Bristow, R. G., Bulbul, M., et al. (2022) · European Urology · doi:10.1016/j.eururo.2022.04.002 · Cited by 130 · see citing works
Self-citationFizazi, K., & Gillessen, S. (2023) · Annals of Oncology · doi:10.1016/j.annonc.2023.02.015 · Cited by 119 · see citing works
Self-citationAnnala, M., Fu, S., Bacon, J. V. W., Sipola, J., Iqbal, N., Ferrario, C., Ong, M., Wadhwa, D., Hotte, S. J., Lo, G., et al. (2021) · Annals of Oncology · doi:10.1016/j.annonc.2021.03.205 · Cited by 73 · see citing works
Self-citationReal-World Genetic Testing Patterns in Metastatic Castration-Resistant Prostate Cancer
Shore, N., Ionescu-Ittu, R., Yang, L., Laliberté, F., Mahendran, M., Lejeune, D., Yu, L., Burgents, J., Duh, M. S., & Ghate, S. R. (2021) · Future Oncology · doi:10.2217/fon-2021-0153 · Cited by 36 · see citing works
Self-citationLampe, H., Tam, L., & Hansen, A. R. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1399802 · Cited by 21 · see citing works
Mattana, F., Muraglia, L., Barone, A., Colandrea, M., Saker Diffalah, Y., Provera, S., Cascio, A. S., Omodeo Salè, E., & Ceci, F. (2024) · Cancers · doi:10.3390/cancers16091643 · Cited by 16 · see citing works
Maurice Dror, C., Chi, K. N., & Khalaf, D. J. (2021) · Translational Andrology and Urology · doi:10.21037/tau-20-1341 · Cited by 14 · see citing works
Self-citationWright, A. A., Poort, H., Tavormina, A., Schmiege, S. J., Matulonis, U. A., Campos, S. M., Liu, J. F., Slivjak, E. T., Gilmour, A. L., Salinger, J. M., et al. (2023) · Gynecologic Oncology · doi:10.1016/j.ygyno.2023.08.020 · Cited by 11 · see citing works
Huang, M., Chen, L., Ma, X., & Xu, H. (2024) · Cancer Cell International · doi:10.1186/s12935-024-03542-8 · Cited by 9 · see citing works
“In PCa, olaparib has gained attention for its effectiveness in patients with mutations in DNA repair genes, offering a targeted treatment approach [28, 30].”
BackgroundHelissey, C., Parnot, C., Rivière, C., Duverger, C., Schernberg, A., Becherirat, S., Picchi, H., Le Roy, A., Vuagnat, P., Pristavu, R., et al. (2023) · Frontiers in Digital Health · doi:10.3389/fdgth.2023.1104700 · Cited by 7 · see citing works
- Authors
- Hussain, M., Mateo, J., Fizazi, K., Saad, F., Shore, N., Sandhu, S., Chi, K. N., Sartor, O., Agarwal, N., Olmos, D., Thiery-Vuillemin, A., Twardowski, P., Roubaud, G., Özgüroğlu, M., Kang, J., Burgents, J., Gresty, C., Corcoran, C., Adelman, C. A., & de Bono, J.
- Affiliations
- Northwestern University (US)
- From the Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago (M.H.); 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 Instituto de Investigación Biomédica de Málaga, Málaga (D.O.) — all in Spain; Institut Gustave Roussy, University of Paris Saclay, Villejuif (K.F.), the Department of Medical Oncology, Centre Hospitalier Universitaire...
- Université Paris-Saclay (FR)
- BC Cancer Agency (CA)
- Tulane University (US)
- AstraZeneca (United Kingdom) (GB)
- Institute of Cancer Research (GB)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-12-10
- Volume
- 383
- Issue
- 24
- Pages
- 2345-2357
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3087416729
- Cited by
- 792
- References
- 2
- Citations by year
- 2026: 75 · 2025: 119 · 2024: 157 · 2023: 150 · 2022: 156 · 2021: 125 · 2020: 8
- FWCI
- 39.64
- 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 (NA)
- Merck Sharp & Dohme (NA)
- 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, overall survival, PARP inhibitors, enzalutamide, abiraterone, crossover, BRCA1, BRCA2, ATM, TP53, PALB2, FANCM, FANCD2, FANCG
- MeSH terms
- Aged, Aged, 80 and over, Antineoplastic Agents, Bridged-Ring Compounds, Humans, Male, Middle Aged, Mutation, Neoplasm Metastasis, Phthalazines, Piperazines, Survival Analysis, Cyclin-Dependent Kinases, Genes, BRCA1, Taxoids, Ataxia Telangiectasia Mutated Proteins, Prostatic Neoplasms, Castration-Resistant
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
