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Highlights from The 2026 American Society of Clinical Oncology (ASCO) Annual Meeting
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PROTEUS Trial: Neoadjuvant Apalutamide and Androgen Deprivation Therapy in High-Risk Localized Prostate Cancer
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Mary-Ellen Taplin, MD
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| Mary-Ellen Taplin presents PROTEUS trial results. The study enrolled 2,100 very high-risk localized prostate cancer patients undergoing radical prostatectomy, randomized to perioperative apalutamide plus ADT versus placebo plus ADT.
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| Perioperative (Neoadjuvant and Adjuvant) Apalutamide + ADT Versus Placebo + ADT with Radical Prostatectomy in High-Risk Localized or Locally Advanced Prostate Cancer: Final Analysis of the PROTEUS Phase 3 Study
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| Mary-Ellen Taplin, MD
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| Mary-Ellen Taplin presented the final analysis of PROTEUS, the largest phase 3 trial in localized prostate cancer, showing that perioperative apalutamide plus ADT before and after radical prostatectomy significantly improved pathologic and clinical outcomes in high-risk/locally advanced disease. A 9-fold higher pathologic complete response/minimal residual disease rate and a 20% reduction in metastasis or death, with additional benefits including 29% lower risk of event/recurrence or death and nearly 3 extra years before needing subsequent therapy, despite a manageable increase in grade 3/4 adverse events.
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| Discussant - The PROTEUS Journey: Setting a New Course for High-Risk Prostate Cancer
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| Declan Murphy, MB, BCh, BaO, FRACS, FRCS Urol
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| Declan Murphy presented a discussant overview of the PROTEUS trial, emphasizing it as a landmark surgical trial establishing perioperative apalutamide plus ADT as a new benchmark for systemic intensification in high-risk localized prostate cancer. The trial’s clinically meaningful gains—9-fold higher pCR/MRD, 20% lower risk of metastasis/death, and ~2.7-year delay in subsequent therapy—support perioperative ADT plus apalutamide becoming a new standard for very high-risk patients undergoing radical prostatectomy, while awaiting mature overall survival data and further subgroup/quality-of-life analyses.
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| Final Results from ZZFIRST: A Randomized Phase 2 Trial of Enzalutamide and Talazoparib in mHNPC
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| Joaquin Mateo, MD, PhD
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| Joaquin Mateo presented final results from ZZFIRST, a randomized phase 2 trial of enzalutamide plus ADT with or without talazoparib in high-volume metastatic hormone-naïve prostate cancer, showing high PSA <0.2 ng/mL response rates at 12 months in both arms but no statistically significant difference. Adding talazoparib improved PSA progression-free survival numerically but increased toxicity substantially—including dose interruptions, discontinuations, and two MDS/AML cases—and translational analyses did not show enzalutamide inducing a functional “BRCAness” phenotype.
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| Fuzuloparib Combined with Abiraterone Acetate and Prednisone as First-Line Treatment for mCRPC: Interim Results from the FUZUPRO Trial
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| Dingwei Ye, MD, PhD
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| Dingwei Ye presented interim results from the phase 3 FUZUPRO trial showing that adding fuzuloparib to abiraterone acetate plus prednisone significantly improved radiographic progression-free survival in first-line metastatic castration-resistant prostate cancer. The benefit was especially large in patients with DDR deficiency (including BRCA1/2 mutations), while overall survival was not harmed and the safety profile was manageable with expected PARP inhibitor toxicities.
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| PARPi-Palooza: Sorting Out the Many Options in Prostate Cancer
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| David Olmos, MD, PhD
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| David Olmos presented a discussant overview of recent PARP inhibitor–ARPI combination data in prostate cancer, emphasizing that benefit is strongest and biomarker-driven in HRR-deficient tumors. TALAPRO-3 and FUZUPRO support ARPI+PARPi as standard for BRCA1/2-mutated mCSPC and mCRPC, while ZZFIRST translational data argue against AR inhibition inducing a true “BRCAness” phenotype, so using these combinations in HRR-competent disease lacks clear mechanistic rationale and must be weighed against added toxicity.
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| Practice Patterns and Outcomes by Genomic Risk in Octogenarians with High-Risk Localized Prostate Cancer: A National Real-World Data Analysis
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| Zachary Moore, MD, PhD
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| Zachary Moore presented a national real-world study of 1,519 octogenarians with high/very high-risk localized prostate cancer showing that Decipher genomic classifier risk was strongly associated with both management choices and outcomes. Even among NCCN high-risk patients, those with genomic classifier–low disease were observed more often and still had excellent outcomes with <5% 5-year metastasis risk, while genomic classifier–high/intermediate risk was linked to more treatment and worse metastasis-free and overall survival.
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| COMRADE: Quality of Life Analysis from a Multicenter, Randomized, Phase 2, Investigator-Initiated ETCTN Trial of Olaparib + Radium-223 Versus Radium-223 in mCRPC with Bone Metastases
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| Rana McKay, MD
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| Rana McKay presented a quality-of-life analysis from the phase 2 COMRADE trial showing that adding olaparib to radium-223 did not significantly worsen patient-reported quality of life or pain compared with radium-223 alone in mCRPC with bone metastases. FACT-P total scores and BPI pain severity showed no meaningful between-arm differences at 12 or 24 weeks, and although radium-223 alone showed slightly better pain interference improvement at week 12, this was not sustained by week 24, supporting the combination’s tolerability despite its superior radiographic progression-free survival.
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| Real-World Use of Olaparib in US Veterans with mCRPC: Treatment Patterns and Outcomes
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| Christelle McFarland, MD
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| Christelle McFarland presented a retrospective VHA study of 477 veterans with mCRPC treated with olaparib, showing that most received it in late-line settings after prior ARPIs, with median time to next therapy of 7 months and median overall survival of 12 months. Outcomes were favorable despite an older, heavily pretreated cohort with higher Black/Hispanic representation than trials, and earlier olaparib use after the first novel hormonal agent was associated with longer median overall survival.
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| Real-World Characteristics, HRR Mutation Testing, Treatment Patterns, and Outcomes of Patients with mCSPC in the US Community Oncology Setting
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| Manojkumar Bupathi, MD, MS
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| Manojkumar Bupathi presented a real-world US community oncology study of 300 mCSPC patients with HRR mutation testing, showing that HRR-mutated patients had numerically shorter overall survival and progression-free survival than non-HRR patients. Median OS was 44.0 vs 48.5 months and median rwPFS was 17.5 vs 22.6 months overall, with the worst outcomes in HRRm patients presenting de novo, supporting early HRR testing and consideration of earlier targeted therapies like PARP inhibitor–ARPI combinations for this higher-risk group.
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| Independent Validation of a Model to Predict Early Favorable PSA Response (NADIR Model) in Enzalutamide-Treated Patients of the ARCHES Trial
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| Soumyajit Roy, MD
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| Soumyajit Roy validated the NADIR model in enzalutamide-treated mHSPC patients from ARCHES, showing it accurately predicts early favorable PSA response. The key findings were an AUC of 0.80 with 92% response in the highest predicted-probability tertile versus 37% in the lowest, and significantly worse overall survival for lower tertiles, supporting its potential as a clinically useful prognostic tool.
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| CLEARED: Comeback from Long Course ADT with Relugolix and Darolutamide in Hormone-Sensitive Prostate Cancer
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| Atish Choudhury, MD, PhD
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| Atish Choudhury presented initial results from the phase 2 CLEARED trial showing that relugolix plus darolutamide was safe and well-tolerated for 6 cycles in high-risk localized, node-positive, or low-volume metastatic hormone-sensitive prostate cancer, with pharmacokinetics similar to historical monotherapy. The key findings were that all 33 patients achieved castrate testosterone and profound PSA declines by cycle 7, with no treatment discontinuations, while the primary endpoint of testosterone recovery by 18 months post-treatment is still being followed.
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| Evaluation of Concomitant Medications in Advanced Prostate Cancer Patients Receiving Apalutamide: TITAN and SPARTAN Post-Hoc Analysis
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| Neeraj Agarwal, MD, FASCO
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| Neeraj Agarwal presented a post-hoc analysis of TITAN and SPARTAN showing that concomitant medications commonly used in advanced prostate cancer did not increase serious adverse events with apalutamide plus ADT. The 2 key takeaways were that treatment-emergent serious adverse events remained low across all medication classes and there were no clinically meaningful drug-drug interaction signals, supporting safe co-administration of apalutamide with these medications under routine monitoring.
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