Niazi on Practice-Changing Data in Prostate Cancer from ESMO 2026

Adding darolutamide (Nubeqa) to androgen deprivation therapy (ADT) and definitive or salvage radiation therapy significantly improved metastasis-free survival by conventional imaging (MFS-CI) in patients with very high-risk localized prostate cancer, according to a planned interim analysis of the phase 3 DASL-HiCaP trial (ANZUP1801; NCT04136353) presented by Tamim Niazi, MDCM, of McGill University and the Jewish General Hospital in Montreal, during the presidential symposium at the 2026 ESMO Congress.

The placebo-controlled trial randomized 1106 patients 1:1 to darolutamide (600 mg twice daily) or placebo for 96 weeks, each with 96 weeks of ADT and radiation therapy to the prostate or prostate bed and pelvic lymph nodes. Of the participants, 935 (84.5%) received primary radiation and 171 (15.5%) received salvage radiation after prostatectomy. Median age was 70 to 71 years, 71% to 74% had Gleason scores of 9 or 10, and 29% had pelvic nodal involvement. MFS-CI was the primary end point, and the interim analysis was triggered after 87 events (67% of 130 planned).

Darolutamide reduced the risk of metastasis or death by 58% (HR, 0.42; 95% CI, 0.27-0.66; P = .0001), crossing the prespecified rejection boundary of .012. There were 27 MFS-CI events (5%) with darolutamide vs 63 (11%) with placebo, and 4-year MFS-CI rates were 95% vs 88%. Benefit was consistent across prespecified subgroups, including pelvic nodal involvement, age, and Gleason score. Secondary end points favored darolutamide, including PSA progression-free survival (HR, 0.47; 95% CI, 0.33-0.67), time to castration resistance (HR, 0.22; 95% CI, 0.09-0.52), and time to subsequent hormonal therapy (HR, 0.36; 95% CI, 0.21-0.60). OS was not significantly different at this interim analysis (HR, 0.88; 95% CI, 0.49-1.59), with 21 vs 24 deaths.

AEs of special interest occurred at similar rates, including vasodilatation and flushing (66% vs 64%) and fatigue (64% vs 57%). Fewer patients in the darolutamide arm received subsequent anticancer therapy (4% vs 10%).

REFERENCE

Niazi T et al. Darolutamide with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiation therapy (RT) for localised, very high-risk prostate cancer: interim analysis of an international, placebo-controlled, randomised phase 3 trial (DASL-HiCaP; ANZUP1801). Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract LBA4.