{"entity":{"id":"paper-nct04821622-n-engl-j-med-2026","kind":"paper","name":"PARP and Androgen-Signaling Inhibition plus ADT in Metastatic Prostate Cancer","aka":[],"tldr":"Published report from the TALAPRO-3 trial registered as NCT04821622, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: A previous trial involving patients with metastatic prostate cancer that was resistant to androgen pathway modulation (formerly referred to as castration-resistant) showed that adding talazoparib to enzalutamide significantly improved imaging-based progression-free survival and overall survival, with the greatest benefit observed in the cohort with alterations in homologous recombination repair genes.\n\nMethods: In this ongoing, phase 3, double-blind trial assessing talazoparib in patients with metastatic androgen pathway modulation-sensitive [APMS] prostate cancer harboring alterations in homologous recombination repair genes, we randomly assigned patients in a 1:1 ratio to receive talazoparib at a dose of 0.5 mg plus enzalutamide at a dose of 160 mg once daily (talazoparib group) or placebo plus enzalutamide at a dose of 160 mg once daily (control group). Randomization was stratified according to disease status (new or relapsed), disease volume (high or low), and BRCA (vs. non- BRCA) mutation status. The primary end point was investigator-assessed imaging-based progression-free survival. The key secondary end point was overall survival.\n\nResults: A total of 300 patients were assigned to the talazoparib group and 299 to the control group. At 3 years, progression-free survival was 77% in the talazoparib group and 56% in the control group (hazard ratio for disease progression or death, 0.48; 95% confidence interval [CI], 0.36 to 0.65; P<0.001). In this interim analysis, overall survival at 3 years was 78% in the talazoparib group and 72% in the control group (hazard ratio for death, 0.77; 95% CI, 0.56 to 1.04). Serious adverse events were reported in 42% and 32% of the patients in the talazoparib group and the control group, respectively. In the talazoparib group, the most common adverse events were anemia, fatigue, and decreased neutrophil count, and the most common event of grade 3 or higher was anemia, reported in 51% of the patients; two treatment-related deaths occurred.\n\nConclusions: Talazoparib added to enzalutamide led to significantly better imaging-based progression-free survival than placebo plus enzalutamide among patients with metastatic APMS prostate cancer harboring alterations in homologous recombination repair genes. Serious adverse events were more common with talazoparib plus enzalutamide than with placebo plus enzalutamide. (Funded by Pfizer; TALAPRO-3 ClinicalTrials.gov number, NCT04821622.).\n\nIndexed on Europe PMC as PubMed record 42223064 (DOI 10.1056/nejmoa2604126). Its abstract cites the registry id NCT04821622, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2026","url":"https://doi.org/10.1056/nejmoa2604126"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42223064/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42223064"},{"label":"ClinicalTrials.gov NCT04821622","url":"https://clinicaltrials.gov/study/NCT04821622"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04821622"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/nejmoa2604126","pmid":"42223064","authors":"Agarwal N, Matsubara N, Azad AA, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04821622 with the most citations, so it is the natural first reading for anyone following the TALAPRO-3 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-nct04821622-n-engl-j-med-2026/","neighbours":{"trial":[{"id":"nct04821622","kind":"trial","name":"Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated mCSPC","route":"/trials/nct04821622/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}