Updated results were also reported on other key end points, including time to pain progression, first symptomatic skeletal event, and initiation of chemotherapy.
Final overall survival data (OS) from the phase 3 ARAMIS trial showed that adding darolutamide (Nubeqa) to androgen deprivation therapy (ADT) led to a 31% reduction in the risk of death compared with ADT alone in patients with nonmetastatic castration-resistant prostate cancer (CRPC), according to results published in the New England Journal of Medicine.1
At a median follow-up of 29 months, the 3-year OS rates were 83% and 77% in the darolutamide and placebo arms, respectively (HR, 0.69; P = .003). This OS benefit was reached even though over half (56%) of the patients on the control arm received darolutamide (n = 170) or other subsequent treatments (docetaxel, abiraterone acetate [Zytiga], enzalutamide [Xtandi], sipuleucel-T [Provenge], and cabazitaxel [Jevtana]) after the study was unblinded.
“Through ongoing research, we have established the importance of focusing treatments on extending lives and limiting side effects for men living with [nonmetastatic] CRPC. With these encouraging darolutamide results, physicians are further armed to treat based on the multiple needs of this patient population including efficacy, delaying morbidity and treatment tolerability,” lead investigator Karim Fizazi, MD, PhD, professor of medicine at the Institut Gustave Roussy, Villejuif, France, state in a press release.2
The double-blind ARAMIS trial included 1509 patients with nonmetastatic CRPC. Patients were randomized in a 2:1 ratio to receive oral darolutamide at 600 mg twice daily plus ADT (n = 955) or placebo plus ADT (n = 554). Patients had an ECOG performance status of 0 to 1. The primary end point of the trial was metastasis-free survival (MFS), with OS as a key secondary end point.
In addition to improving OS, the darolutamide regimen also led to statistically significant delays in the time to first symptomatic skeletal event (HR, 0.48; P = .005), time to pain progression (HR, 0.65; P <.001), and time to initiation of chemotherapy (HR, 0.58; P <.001).
The previously reported primary analysis of ARAMIS showed a highly significant MFS benefit with darolutamide. The darolutamide regimen reduced the risk of metastases or death by 59% versus ADT alone, with a median MFS of 40.4 months versus 18.4 months, respectively (HR, 0.41; P <.001).These results led to the July 2019 FDA approval of darolutamide for the treatment of patients with nonmetastatic CRPC.
Regarding safety, the final analysis found that treatment-related adverse events (TRAEs) occurred in 85.7% and 79.2% of the darolutamide and control arms, respectively. Grade 3/4 TRAEs occurred in 26.3% versus 21.7%, respectively.
Serious TRAEs were experienced by 26.1% and 21.8% of the darolutamide and control arms, respectively. TRAEs led to treatment discontinuation in 9% of both study arms. The mortality rate was 4% with darolutamide and 3.4% with ADT alone.
Of note, a separate subgroup analysis of the ARAMIS trial that was recently reported showed that darolutamide is effective for the treatment of high-risk patients with nonmetastatic CRPC who have a rapid PSA doubling time (PSADT).3 Among patients with a PSADT ≤6 months, darolutamide plus ADT reduced the risk of metastases or death by 59% versus ADT alone (HR, 0.41). This benefit was similar to that observed in patients with a PSADT >6 months, in whom there was a 62% reduction in the risk of metastases or death (HR, 0.38).
1. 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
2. New England Journal of Medicine Publishes Final Data for NUBEQA® (darolutamide) Plus Androgen Deprivation Therapy Showing a Statistically Significant Improvement in Overall Survival in Men with Non-Metastatic Castration-Resistant Prostate Cancer. Published September 9, 2020. https://bwnews.pr/3bKGwd6. Accessed September 10, 2020.
3. Bögemann MWH, Shore ND, Tammela TLJ, et al. Efficacy and safety of darolutamide (DARO) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and a prostate-specific antigen doubling time (PSADT) >6 months. 2020 European Association of Urology Virtual Congress. July 17-26, 2020. Abstract 919