ASCO 2022: DARolutamide ObservationaL (DAROL) Study in Patients with Nonmetastatic Castration-Resistant Prostate Cancer

( At the 2022 American Society of Clinical Oncology Annual Meeting held in Chicago and virtually, the poster session focused on Prostate, Testicular, and Penile cancers on Monday afternoon included a presentation from Dr. Evan Yu examining real world outcomes for patients treated with darolutamide in advanced prostate cancer.

Darolutamide is a structurally distinct and highly potent androgen receptor inhibitor. Like apalutamide and enzalutamide, a randomized clinical trial of darolutamide (ARAMIS, NCT02200614) demonstrated significantly increased median metastasis-free survival by ̃2 years and improved overall survival in men with non-metastatic castration resistant prostate cancer (nmCRPC), with a favorable tolerability profile. Further, in the ARASENS trial, triplet therapy with darolutamide, docetaxel, and ADT improved overall survival compared to docetaxel and ADT. Moving from the clinical trial space into real-world practice, the ongoing DAROL trial (NCT04122976) was designed to support results from ARAMIS and to provide insight into the safety and effectiveness of darolutamide and the management of nmCRPC in the real-world setting. At this year’s ASCO meeting, Dr. Yu provided the results of the first prespecified interim analysis of this study.

Dr. Yu outlined that DAROL is an international, single-arm, non-interventional study (NCT04122976). The study is accruing eligible patients with confirmed nmCRPC who have not yet received darolutamide but for whom the decision to treat with darolutamide was made before enrollment. Further, patients have to be at least 18 years of age. Patients are treated with darolutamide with treatment dose and duration at the discretion of the investigator’s routine practice. The primary endpoint is safety, including treatment-emergent adverse events (TEAEs). Prostate-specific antigen (PSA) response was an exploratory objective.

In this abstract, the authors provide descriptive statistics for the first prespecified interim analysis with a data cutoff of September 23, 2021, including the first 100 patients (from US, Canada, Japan) who had completed at least 6 months of treatment or discontinued treatment.

All 100 patients were evaluable for safety. This cohort had a median age of 78.0 years. The majority (59%) were White with 11% Black, 27% Asian and 1% and 2%, respectively, for other and not reported race. The preponderance of the cohort (79%) was from North America with the remaining 21% from Asia Pacific. At baseline, 72% of patients had an ECOG performance status of 0–1 with 5% have a performance status of 2–4 and no data available for 23% of patients.

In terms of disease characteristics, the median time from initial prostate cancer diagnosis to the development of castration-resistant disease was 89.1 months (quartile 1: 39.1 to quartile 3: 130.6 months). Further, the Gleason score at initial diagnosis ≤6 in 15.8%, 7 in 38.9% and 8–10 in 45.3% of participants. At baseline, 75.3% of patients had a PSA of 10ng/mL or less. In terms of PSA kinetics, PSA doubling time was 6 months or less in 58.2% and more than 6 months in the remaining 41.8%.

In terms of treatment characteristics, the median duration of treatment was 11.3 months with an interquartile range of 8.4 to 14.4 months. Median starting dose and daily treatment dose was 1200 mg daily.

Over a median follow-up time of 12.3 month (interquartile range 9.6–15.6 months), 28% of patients had TEAEs of any grade. More serious adverse events were uncommon with 3% grade 3 events and no grade 4 or 5 events observed. In total, 2% of patients had serious adverse events (AEs). TEAEs led to permanent study drug discontinuation in 7% of patients. These real-world data were in keeping with the safety profile observed in ARAMIS.

In terms of specific treatment-related adverse events occurring in 2% of patients or more, the following were relatively common events: fatigue (5%), diarrhea (5%), asthenia (2%), muscle weakness (2%), anemia (2%), and rash (including rash pruritic, 2%).

Among 93 patients who were evaluable for efficacy, PSA responses of ≥30%, ≥50%, and ≥90% at any time during follow-up were 81.7%, 77.4% and 52.7%, respectively.

Thus, Dr. Yu concluded that this first interim analysis of the DAROL observational study demonstrates that safety and tolerability of darolutamide in real-world practice was consistent with the favorable tolerability profile observed in the randomized ARAMIS trial.

Presented by: Evan Yu, MD, Professor, Department of Medicine, Division of Oncology, University of Washington School of Medicine. Member, Clinical Research Division, Fred Hutchinson, Cancer Research Center, Clinical Research Director, Genitourinary Oncology, Seattle Cancer Care Alliance, Medical Director, Clinical Research Service, F

Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022.


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