Neal Shore, MD, discusses results from the open-label rollover study from the phase 3 ARAMIS trial, which he presented at the 2023 Genitourinary Cancers Symposium.
Neal D. Shore, MD, FACS, director of the Carolina Urologic Research Center, Atlantic Urology Clinics in Myrtle Beach, South Carolina, discusses the open-label (OL) rollover study (ROS) from the phase 3 ARAMIS trial, which he presented at the 2023 Genitourinary Cancers Symposium.1
Darolutamide (Nubeqa) was approve by the FDA in 2019 for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC) based on findings from the phase 3 ARAMIS trial (NCT02200614), a double-blind (DB), randomized, multicenter study.2
In the original ARAMIS trial, adding darolutamide to androgen-deprivation therapy (ADT) reduced the risk of death by 31% compared with ADT plus placebo in men with nmCRPC (HR, 0.69; 95% CI, 0.53-0.88; P = .003).3 The primary analysis of the study showed that adding darolutamide to ADT also led to a 59% reduction in the risk of metastases or death (HR, 0.41; 95% CI, 0.34-0.50; P <.001) versus ADT alone.2
The ARAMIS study was unblinded following the primary analysis of DB treatment, with all patients being allowed to continue on OL darolutamide. Following the completion of the original ARAMIS trial, patients with no evidence of metastases who were clinically benefiting from darolutamide had the option to continue receiving darolutamide in the ROS. Of the 954 patients who started treatment on darolutamide on randomization in the original ARAMIS trial, 466 continued to OL DARO and 294 (31%) entered the ROS.
The median treatment duration was 1.5 years for patients in the DB period (range, 0.0-4.0); 2.1 years for patients in the DB and OL periods (range, 0.0-4.9); and 2.8 years for patients in DB, OL, and ROS periods (range, 0.0-6.8). By the data cut-off date of January 31, 2023, 30% of patients had received darolutamide for at least 4 years, and 24% of patients were still receiving darolutamide.
Incidence of treatment-related AEs (TEAEs) increased slightly over time, “as expected with longer observation time,” the investigators noted. In total, 85.7%, 89.8%, and 91.5% of patients in the DB, DB and OL, and DB/OL/ROS periods, respectively, experienced an any-grade TEAE. In addition, 26.3%, 31.8%, and 35.5% of patients in the DB, DB and OL, and DB/OL/ROS periods, respectively, experienced a grade 3/4 TEAE. Further, 26.1%, 32.1%, and 38.5% of patients, respectively, experienced a serious TEAE, and 8.9%, 10.5%, and 12.9% of patients experienced a TEAE leading to treatment discontinuation. The investigators did not identify any new safety concerns in patients who entered the ROS.
In the video, Shore comments that the ROS data, “really demonstrate how well-tolerated the drug is.”
1. Shore ND, de Almeida Luz M, Ulys A, et al. Long-term safety and tolerability of darolutamide and duration of treatment in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) from the ARAMIS Rollover Study. Presented at: 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium; February 16-18, 2023; San Francisco, CA. Abstract 147.
2. FDA approves darolutamide for non-metastatic castration-resistant prostate cancer. Published online July 30, 2019. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-non-metastatic-castration-resistant-prostate-cancer
3. Fizazi K, Shore N, Tammela TL, et al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med. 2020;383(11):1040-1049. doi: 10.1056/NEJMoa2001342