“These results provide compelling evidence for early darolutamide (Nubeqa) treatment in men with nonmetastatic CRPC,” lead study author Dr. Karim Fizazi, said in a virtual presentation during the meeting.
The addition of Nubeqa (darolutamide) to androgen deprivation therapy (ADT) demonstrated a significant overall survival improvement compared to placebo and ADT in patients with nonmetastatic castration-resistant prostate cancer (CRPC), according to data from the phase 3 ARAMIS trial presented during the 2020 ASCO Virtual Scientific Program.
The data also showed that adding Nubeqa to ADT significantly delayed the beginning of cancer-related symptoms such as pain, as well as the initiation of chemotherapy to treat the patient population.
“These results provide compelling evidence for early darolutamide treatment in men with nonmetastatic CRPC,” lead study author Dr. Karim Fizazi, a professor of medicine at the Institut Gustave Roussy in France, said in a virtual presentation during the meeting. “Darolutamide provides clinical benefits, in addition to prolonging survival for men with M0 CRPC, for whom the development of metastases can cause cancer-related symptoms that affect their daily lives or impose a burden of additional treatments.”
Based on earlier findings of the ARAMIS trial, the Food and Drug Administration in 2019 approved Nubeqa to treat patients with nonmetastatic CRPC. Nubeqa is a structurally distinct androgen receptor (AR) inhibitor with low blood—brain barrier penetration and low potential for drug to drug infection.
Fizazi and colleagues presented data from the double-blind, placebo-controlled, multicenter phase 3 trial in which investigators assessed the efficacy and safety of Nubeqa in combination with ADT in 1,509 patients with nonmetastatic CRPC who were receiving a concomitant gonadotropin-releasing hormone analog or had surgery to remove both testicles.
The investigators randomized patients to receive either 600 milligrams (mg) of Nubeqa orally twice a day plus ADT (955) or placebo plus ADT (554). Metastasis-free survival (MFS), which is the time from the beginning of treatment a patient is alive, and the cancer has not spread, served as the study’s primary outcome.
Additional secondary endpoints included overall survival (OS), time to pain progression, time to the start of first cytotoxic chemotherapy, time to first symptomatic skeletal event, and characterization of the safety and tolerability of study drug.
At the primary analysis, patients who received Nubeqa achieved a median MFS of 40.4 months compared to 18.4 months in those who received placebo. After a median follow-up of approximately 29 months, the three-year OS rates were 83% and 77% within the Nubeqa and placebo arms, respectively.
Prior to the final analysis, the investigators unblinded the study. Following the unblinding, 170 patients who were initially randomized to receive placebo crossed over to the Nubeqa arm. Additional findings demonstrated that even though 56% of patients initially randomized to placebo switched to receive Nubeqa or another life-prolonging therapy, there was still an OS benefit.
Patients who received the study drug also experienced a significant delay to the time of pain progression (40.3 months) compared to those who received placebo (25.4 months). The safety profile of Nubeqa was similar to other previous analyses of the drug. Treatment-associated side effects such as fatigue, bone fracture, decreased weight and rash were not statistically different between the two patient populations, according to Fizazi.
Interim findings from the trial previously demonstrated intriguing quality-of-life (QOL) data associated with Nubeqa among this patient population. Additional ARAMIS findings showed that the study drug maintained QOL and led to a 35% reduction in the risk of pain progression vs. placebo in this patient population.
Nubeqa is also being evaluated in an international, double-blind, placebo-controlled, phase 3 ARASENS study, which is exploring Nubeqa plus ADT in combination with docetaxel in approximately 1,300 patients with newly diagnosed, metastatic hormone-sensitive prostate cancer.
A version of this story originally appeared on OncLive® as “Darolutamide Improves OS, Delays Onset of Cancer-Related Morbidity and Subsequent Chemo in Nonmetastatic CRPC”.