Abstract | BACKGROUND: METHODS: We conducted a randomized, open-label, phase 3 trial evaluating the PARP inhibitor olaparib in men with metastatic castration-resistant prostate cancer who had disease progression while receiving a new hormonal agent (e.g., enzalutamide or abiraterone). All the men had a qualifying alteration in prespecified genes with a direct or indirect role in homologous recombination repair. Cohort A (245 patients) had at least one alteration in BRCA1, BRCA2, or ATM; 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:
|
Authors | Johann de Bono, Joaquin Mateo, Karim Fizazi, Fred Saad, Neal Shore, Shahneen Sandhu, Kim N Chi, Oliver Sartor, Neeraj Agarwal, David Olmos, Antoine Thiery-Vuillemin, Przemyslaw Twardowski, Niven Mehra, Carsten Goessl, Jinyu Kang, Joseph Burgents, Wenting Wu, Alexander Kohlmann, Carrie A Adelman, Maha Hussain |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 382
Issue 22
Pg. 2091-2102
(05 28 2020)
ISSN: 1533-4406 [Electronic] United States |
PMID | 32343890
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2020 Massachusetts Medical Society. |
Chemical References |
- Androstenes
- Antineoplastic Agents
- Benzamides
- Nitriles
- Phthalazines
- Piperazines
- Poly(ADP-ribose) Polymerase Inhibitors
- Phenylthiohydantoin
- enzalutamide
- ATM protein, human
- Ataxia Telangiectasia Mutated Proteins
- abiraterone
- olaparib
|
Topics |
- Aged
- Aged, 80 and over
- Androstenes
(adverse effects, therapeutic use)
- Antineoplastic Agents
(adverse effects, therapeutic use)
- Ataxia Telangiectasia Mutated Proteins
(genetics)
- Benzamides
- Genes, BRCA1
- Genes, BRCA2
- Humans
- Loss of Function Mutation
- Male
- Middle Aged
- Neoplasm Metastasis
(drug therapy)
- Nitriles
- Phenylthiohydantoin
(adverse effects, analogs & derivatives, therapeutic use)
- Phthalazines
(adverse effects, therapeutic use)
- Piperazines
(adverse effects, therapeutic use)
- Poly(ADP-ribose) Polymerase Inhibitors
(adverse effects, therapeutic use)
- Progression-Free Survival
- Prostatic Neoplasms, Castration-Resistant
(drug therapy, genetics, mortality, pathology)
|
|
Join CureHunter, for free Research Interface BASIC access!
Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease.
Find out why thousands of doctors, pharma researchers and patient activists
around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!
|