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Highlights from the American Society of Clinical Oncology 2026 Annual Meeting
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| Early Results of COMPPARE, a Prospective Comparison of Outcomes with Proton and Photon Radiation in Prostate Cancer
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| Nancy Mendenhall, MD, FACR, FASTRO
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| COMPPARE’s early results showed excellent short-term outcomes with both proton therapy and IMRT for localized prostate cancer, with no significant differences in patient-reported quality of life, toxicity, or 3-year freedom from PSA progression. Temporary rectal spacers reduced rectal/bowel toxicity in both groups, and longer follow-up is still needed to see whether proton therapy offers any durable advantage over IMRT.
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| A Phase 1, First-in-Human Study Evaluating the Safety, Pharmacokinetics, and Efficacy of ABBV-969 in Patients with mCRPC
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| Tanya Dorff, MD
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| ABBV-969, a first-in-class dual PSMA/STEAP1 antibody–drug conjugate delivering a topoisomerase-1 inhibitor, showed promising activity and a manageable safety profile in a first-in-human phase 1 dose-escalation study of heavily pretreated mCRPC. At doses ≥3 mg/kg, confirmed PSA50 and PSA90 responses were 67% and 30%, objective response rate was 45% (including liver metastases), median radiographic PFS was 15.3 months, and responses occurred regardless of prior radioligand exposure.
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| Phase 2 Study of YL201, an Anti-B7H3 Antibody-Drug Conjugate, in Heavily Pretreated mCRPC
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| Yao Zhu, MD
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| YL201 (tambotatug pelitecan), a novel B7-H3–targeting ADC with a dual-cleavage mechanism for enhanced bystander effect, showed encouraging activity in heavily pretreated mCRPC: confirmed ORR was 32.8% overall, confirmed PSA50 was 37.2%, median radiographic PFS was 9.9 months, median duration of response was 12.7 months, and 15-month OS was 57.8%.
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| Phase 2 Multicenter Trial of Chemoimmunotherapy for Patients with Neuroendocrine or Aggressive Variant Metastatic Prostate Cancer (CHAMP)
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| Andrew Armstrong, MD, MSc
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| The CHAMP phase 2 trial showed that adding ipilimumab + nivolumab to cabazitaxel–carboplatin improved 6-month radiographic PFS to 74% with median immune-modified rPFS of 12 months and median OS of 12 months in heavily pretreated NEPC/AVPC, including a 23% 2-year OS tail and 37% ORR. The regimen was feasible with mostly grade 1–2 toxicities, supporting further randomized evaluation of chemoimmunotherapy in these aggressive variants.
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| PROTRACT: A Randomized Phase II Trial Comparing ctDNA-Guided Biomarker-Directed Therapy vs Patient/Clinician's Choice for mCRPC Progressing After AAP
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| Corinne Maurice-Dror, MD
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| The PROTRACT phase II trial showed that ctDNA-guided treatment selection significantly improved outcomes vs physician/patient preference in mCRPC progressing after abiraterone: median PFS was 5.6 vs 2.5 months and median OS was 46.3 vs 15.3 months, with higher PSA50 response. The biomarker-directed arm assigned docetaxel for ctDNA ≥2% and enzalutamide for <2%, and while docetaxel had more grade ≥3 toxicity and discontinuations, the overall safety profile was expected with no new signals.
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| ctDNA-Based Clinical-Genetic Prognostic Model for rPFS in Patients with mCRPC: Analysis of Alliance A031201
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| Susan Halabi, PhD
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| This Alliance A031201 analysis developed and validated a machine learning clinical-genetic model that integrates ctDNA-derived genomic features with clinical variables to predict radiographic PFS in first-line mCRPC on enzalutamide ± abiraterone. Adding ctDNA significantly improved predictive accuracy over a clinical-only model with a 30% net reclassification improvement, and the model cleanly stratified patients: low-risk had median rPFS 35.2–40.0 months vs poor-risk 12.8–14.8 months.
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| Canadian Cancer Trials Group (CCTG) Study PR21 (PLUDO): Results of Crossover Treatment from a Randomized Trial of 177Lu-PSMA-617 vs Docetaxel in Patients with mCRPC
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| Kim N. Chi, MD
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| The PLUDO (PR21) crossover analysis showed no significant difference in outcomes between sequencing 177Lu-PSMA-617 then docetaxel versus docetaxel then 177Lu-PSMA-617 in ARPI-pretreated mCRPC: from randomization, rPFS2 was 18.5 vs 15.8 months and OS was 23.2 vs 20 months; from crossover, subsequent PFS was 4.8 vs 5.4 months and OS 8.1 vs 8.3 months. PSA ≥50% declines were higher when crossing to docetaxel after LuPSMA, and toxicity profiles were consistent with each therapy, supporting either sequence after ARPI.
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| Subgroup Analyses by Disease Volume and De Novo/recurrent mHSPC in the PSMAddition Study of 177Lu-PSMA-617
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| Fred Saad, MD, FRCS
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| PSMAddition subgroup analyses showed that adding 177Lu-PSMA-617 to ADT + ARPI provided a consistent rPFS benefit across disease volume and timing subgroups in PSMA-positive mHSPC: high-volume HR 0.72, low-volume HR 0.73, de novo HR 0.74, and recurrent HR 0.74. Similar benefits were seen for time to PSA progression and time to mCRPC, with patient-reported outcomes and safety profiles consistent across subgroups and matching the overall trial results.
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