DASL-HiCaP: darolutamide added to ADT plus radiotherapy gives MFS HR 0.42 in very-high-risk prostate cancer, but no OS difference yet

Data as of 2026-10-25 (Taipei time). [Fact] statements are sourced; [Inference] statements are this article's judgment.

1. One-line conclusion

[Fact] At DASL-HiCaP's interim analysis, adding 96 weeks of darolutamide to ADT plus radiotherapy gave metastasis-free survival by conventional imaging (MFS-CI) HR 0.42 (95% CI 0.27–0.66; P=.0001), with 4-year MFS 95% vs 88%; OS HR 0.88 (0.49–1.59), not significantly different (Targeted Oncology). [Inference] Bayer may be able to take Nubeqa into very-high-risk localized disease, but an absolute difference of 7 percentage points and 90 events mean a sizeable number needed to treat; clinical uptake will depend on OS and cost.

2. What happened

[Fact] DASL-HiCaP (ANZUP1801; NCT04136353) is the international, placebo-controlled, 1:1 randomized Phase 3 trial reported as ESMO 2026 LBA4. 1106 patients were randomized to darolutamide 600 mg twice daily or placebo, each for 96 weeks; both arms received 96 weeks of ADT and radiotherapy to the prostate or prostate bed plus pelvic nodes. 84.5% (935 patients) received definitive radiotherapy and 15.5% (171 patients) salvage radiotherapy after prostatectomy; median age was 70–71 years, Gleason 9–10 accounted for 71–74%, and 29% had pelvic nodal involvement (Targeted Oncology); Fierce gives Gleason 9–10 as 73% (Fierce).

[Fact] The primary endpoint was MFS-CI; the interim analysis was triggered at 87 events (67% of the planned 130), with a rejection boundary of .012. MFS events were 27 (5%) vs 63 (11%), HR 0.42 (0.27–0.66; P=.0001), 4-year MFS 95% vs 88%. Among secondary endpoints, PSA PFS HR 0.47 (0.33–0.67), time to castration resistance HR 0.22 (0.09–0.52), time to subsequent hormonal therapy HR 0.36 (0.21–0.60); OS HR 0.88 (0.49–1.59), with 21 vs 24 deaths. Vasodilation or hot flushes 66% vs 64%, fatigue 64% vs 57%; subsequent anticancer therapy 4% vs 10% (Targeted Oncology). The final analysis of the primary endpoint, 5-year MFS, is expected in 2027 (Fierce). 27+63=90, which differs from the trigger threshold of 87; [Inference] 87 is the trigger threshold and 90 the actual number of events at cutoff, so the difference is reasonable.

For sponsors: with strict high-risk selection, 1100 patients and 90 interim events were enough to read out MFS, so intensification trials in localized prostate cancer need not be sized like trials in metastatic disease.

3. Why it succeeded

[Inference] Patient selection is the first reason. Fierce quotes the trial's co-chair as saying patients had to meet strict "DASL high risk" criteria (Fierce); with Gleason 9–10 above 70% and nearly 30% node-positive (Targeted Oncology), the event rate was high enough to show a difference with limited numbers and follow-up.

[Inference] Darolutamide's tolerability is the second reason. Rates of AEs of special interest such as hot flushes and fatigue were similar between arms (Targeted Oncology), which matters for a population around 70 years old also undergoing radiotherapy, and helps sustain completion of 96 weeks of treatment.

[Inference] OS has not separated because there were only 45 deaths (21 vs 24), giving insufficient power; the higher rate of subsequent therapy in the control arm (10% vs 4%) also dilutes OS (Targeted Oncology). In addition, MFS was assessed by conventional imaging (Targeted Oncology); in the PSMA PET era some patients with micrometastases may have been counted as "metastasis-free", which is the main discount when extrapolating the result to modern practice.

4. Regulatory and commercial implications

[Fact] Bayer has not announced a regulatory plan in this population, saying it must first fully evaluate the data (Fierce); the presentation concluded that MFS-CI is an established surrogate for OS in this setting (Targeted Oncology). [Inference] In curable localized disease, the FDA may require more mature OS or at least evidence of no OS detriment, making the 2027 final analysis (Fierce) the key moment.

[Fact] Nubeqa sales in 2025 were €2.39 billion; Xtandi sales in 2025 were about $6.4 billion, with patents expiring in stages from next year (Fierce). [Inference] If Nubeqa wins a high-risk localized indication, it can secure position before enzalutamide goes generic; Fierce also notes that Nubeqa and Erleada compete directly across several prostate cancer indications (Fierce).

5. Recommendations for the next trial and OncoLattice (GU oncology)

[Inference] First, stage with PSMA PET. DASL-HiCaP's MFS was assessed by conventional imaging (Targeted Oncology); a new trial that does not use PSMA PET for baseline staging will have its population questioned as outdated by reviewers. Sponsors should first survey PSMA PET access across sites; some sites in Taiwan and Asia remain limited.

[Inference] Second, test treatment duration. ARPI and ADT are both currently given for 96 weeks (Targeted Oncology); the next trial could compare 12 vs 24 months, or use an adaptive shortening design based on undetectable PSA, which matters for older patients and for healthcare spending.

[Inference] Third, the salvage population needs a dedicated trial. Salvage radiotherapy patients made up only 15.5%, 171 patients (Targeted Oncology), a small subgroup; PSA recurrence after prostatectomy is the most common scenario in urology and deserves its own design.

[Inference] Fourth, site strategy and endpoints. These trials require collaboration among urology, radiation oncology and nuclear medicine; OncoLattice should screen sites for "existing PSMA PET plus radiotherapy scheduling capacity" and track the time from referral to start of radiotherapy. If MFS is the primary endpoint, confirm with the FDA in advance and make OS and prostate cancer-specific survival key secondary endpoints in hierarchical testing; DASL-HiCaP had only 45 deaths at the interim (Targeted Oncology), showing OS needs longer follow-up.

6. Open questions and what to watch

The final analysis of 5-year MFS and OS is expected to read out in 2027 (Fierce) and will be posted under NCT04136353 (ClinicalTrials.gov); subgroup HRs for definitive vs salvage radiotherapy and node-positive vs node-negative disease, plus quality of life, fractures and cardiovascular events, will most likely appear in the LBA4 full paper, whose journal and date have not been announced; for now there are only ESMO 2026 abstract reports (Targeted Oncology). Bayer says it will decide on a regulatory plan only after fully evaluating the data, and FDA and EMA filing dates have not been announced (Fierce).

The next thing to watch is the 2027 final analysis: if OS still does not separate, whether the FDA accepts MFS in localized disease will set the endpoint precedent for all ARPI intensification trials.

Evidence limitations

The interim analysis has only 90 MFS events and 45 deaths, and the HR CI is wide (0.27–0.66) (Targeted Oncology); ClinicalTrials.gov lists actual enrollment of 1100, slightly different from the reported 1106 (ClinicalTrials.gov).

Advice for readers: sponsors planning high-risk localized prostate cancer trials who use DASL-HiCaP's 4-year MFS of 88% as the control-arm assumption should also account for PSMA PET staging changing the baseline population, and keep endpoint choice flexible until the 2027 final analysis (Fierce).

Note: differences from the original relay

The relayed figures (n=1106, HR 0.42, 95% vs 88%, OS HR 0.88, final analysis 2027) match the sources. CIs and p-values added; the Gleason 9–10 proportion differs slightly between the two sources (71–74% vs 73%).