ASCO 2023: Darolutamide Observational (DAROL) Study in Patients with Nonmetastatic Castration-Resistant Prostate Cancer: Second Interim Analysis.

( The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a prostate, testicular, and penile cancers poster session. Dr. Evan Yu presented the 2nd interim results of DAROL, an observation study evaluating darolutamide use in patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

The use of darolutamide 600 mg twice daily in patients with nmCRPC was shown to improve metastasis-free survival (MFS) by approximately two years (HR: 0.41, 95% CI: 0.34 – 0.50) and reduce the overall mortality rate by 31% (HR: 0.69, 95% CI: 0.53 – 0.88), compared to placebo, with a favorable toxicity/tolerability profile.1 The ongoing DAROL study (NCT04122976) aims to evaluate the real-world safety and effectiveness of darolutamide in patients with nmCRPC.

Dr. Yu reported the results from the pre-planned second interim analysis.

DAROL was a global, open-label, single-arm, non-interventional study in patients aged ≥18 years with confirmed nmCRPC for whom the decision to be treated with darolutamide was decided pre-enrollment.


The primary endpoint is safety, including the incidence, severity, and frequency of treatment-emergent adverse events (TEAEs). Secondary endpoints include:

  • Patient demographics and disease characteristics
  • Treatment duration
  • Metastasis-free survival
  • Overall survival (OS)
  • Time to prostate-specific antigen (PSA) progression
  • PSA response

The primary and secondary endpoints were reported after 300 patients completed ≥6 months of treatment. All treated patients were assessed for safety, while efficacy was evaluated in patients who did not violate any eligibility criteria and had ≥1 post-baseline assessment (cut-off: October 11, 2022).


Of the 300 patients in this study, the enrolment by geographic region was as follows:

  • North America: 45%
  • Europe: 30%
  • Asia Pacific: 25%
  • Latin America: <1%


The median age was 80 years and 92% had a reported ECOG performance status of 0 or 1 at baseline. 51% of patients had Grade Group 4 or 5 disease. The median baseline serum PSA was 3.9 ng/mL (range: 0 – 248.0), with 21% of patients reporting PSA < 2 ng/mL. The median baseline PSA doubling time (PSADT) was 5.3 months (range: 0 – 36.2), with 42% of patients reporting a PSADT >6 months. At the data cut-off, median follow-up time was 14.8 months (IQR: 10.9 – 19.3) and median treatment duration was 13.4 months (IQR: 9.3 – 17.8).

The TEAEs and darolutamide-related TEAES are summarized in the table below. Overall, the incidence of these TEAEs was low, consistent with the safety profile of darolutamide reported in ARAMIS. The most common TEAE was fatigue (8-9% of patients). Grade 3-4 darolutamide-related TEAEs occurred in 4% of patients, with 16 patients (5%) discontinuing darolutamide due to drug-related TEAEs.


For the 263 patients eligible for the efficacy analysis, the median time to PSA progression was 17.6 months (95% CI: 13.2 – 19.0); MFS/OS data remains immature. PSA declines from baseline of ≥30%, ≥50%, and ≥90% at any time were observed in 80%, 76%, and 54% of patients, respectively.

Dr. Yu and colleagues concluded that in the DAROL second interim analysis report, under real-world conditions, darolutamide continued to show a favorable safety profile, consistent with the clinical profile observed in ARAMIS, with no new safety signals.

Presented by: Evan Yu, MD, Section Head of Cancer Medicine in the Clinical Research Division at Fred Hutchinson Cancer Center. He also serves as the Medical Director of Clinical Research Support at the Fred Hutchinson Cancer Research Consortium and is a Professor of Medicine in the Division of Oncology and Department of Medicine at the University of Washington School of Medicine in Seattle, WA

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023. 


  1. Fizazi K, Shore N, Tammela TL, et al. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040-1049.