Nearly all men with non-metastatic castration-resistant prostate cancer (nmCRPC) received the full planned dose of Nubeqa (darolutamide) tablets while participating in the ARAMIS Phase 3 trial, and few required dose adjustments or discontinued treatment, according to a new ad-hoc analysis of the study.
Findings from this analysis were recently presented in an e-poster, titled “Tolerability and treatment response to darolutamide (DARO) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in the phase III ARAMIS trial,” at the ESMO Virtual Congress 2020, held online Sept. 19–21.
The medication works by inhibiting androgen receptors — proteins found on the surface of cells that bind to male hormones — and interrupting the androgen signaling cascade, which promotes the growth of prostate cancer cells.
Nubeqa’s approval last year was based on data from the ARAMIS trial (NCT02200614), which compared the safety and efficacy of Nubeqa plus androgen deprivation therapy (ADT) to those of a placebo plus ADT in a group of 1,509 nmCRPC patients. The trial was funded by Bayer and Orion.
A primary analysis of the study showed that adding Nubeqa to standard ADT prolonged the time patients lived without having their cancer spread from 18.4 to 40.4 months, lowering the risk of cancer spreading or death by 59%.
Nubeqa also prolonged the time patients lived without their disease worsening from 14.8 to 36.8 months, reducing the risk of disease progression or death by 62%.
The incidence of side effects was found to be similar in the two treatment groups. The addition of Nubeqa to ADT did not increase the frequency of serious side effects, such as seizures, falls, bone fractures, or high blood pressure, or the number of discontinuations.
Updated findings from ARAMIS also showed Nubeqa was able to delay the onset of urinary and bowel symptoms, as well as the time men lived without their pain levels worsening.
New data from the ad-hoc analysis now show that nearly all men (97.2%) who received Nubeqa in combination with ADT during ARAMIS were able to take their full planned dose of 600 mg twice daily. This was comparable to the 98.4% of patients who received their entire ADT prescribed treatment regimen.
“In clinical practice, ability to maintain planned dose and schedule are important considerations,” Matthew Smith, MD, PhD, director of the Genitourinary Malignancies Program at Massachusetts General Hospital Cancer Center, said in a press release. “These data support darolutamide’s value as a treatment option in men with nmCRPC.”
The ad-hoc analysis was based on primary and final data from the double-blind treatment period of ARAMIS. It also showed that a relatively low percentage of patients in both groups required dose adjustments during the study, though that percentage was greater in the Nubeqa group (15.2% vs. 9.7%).
But notably, most patients in both treatment groups were able to re-escalate to their full planned dose during the study (91.7% in the Nubeqa group and 88.9% in ADT alone).
Additionally, adding Nubeqa to ADT did not increase the proportion of men who discontinued treatment due to side effects (8.9% vs. 8.7%).
The ad-hoc analysis also found that a higher proportion of men who received Nubeqa in combination with ADT saw their prostate-specific antigen (PSA) levels drop by at least 50% during the study, compared to those who were treated with ADT alone (83.6% vs. 7.6%).
Maximal PSA responses — a drop by 90% or more in PSA levels — were seen in 50.9% of patients receiving Nubeqa, compared with 1.8% of those on ADT only. The majority of patients (95%) attaining such responses remained free of metastasis for at least one year.
“Favorable tolerability of [Nubeqa] at the recommended dose of 600 mg twice daily was associated with low rates of dose reduction and treatment discontinuation, which in turn may lead to extended survival with longer duration of treatment with [Nubeqa],” the investigators wrote. “It is important to further assess the real-world tolerance of different [androgen receptor inhibitors] in men with nmCRPC.”