Long-Term Nubeqa Is Safe, Efficacious in Prostate Cancer Treatment

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Extended-duration Nubeqa reduced the risk of death in patients with nonmetastatic castration-resistant prostate cancer, study results showed.

Extended-duration Nubeqa (darolutamide) — meaning that the drug was given slowly over a long period of time — proved to be safe and efficacious in treating patients with nonmetastatic castration-resistant prostate cancer (CRPC), according to findings from the ARAMIS Rollover Study that were presented at the 2023 American Urological Association (AUA) Annual Meeting.

At the time of data collection on Jan. 31, 2022, 30.1% of patients had received Nubeqa for at least four years and 24% of patients were still on treatment with the androgen receptor (AR) inhibitor.

Additionally, the safety profile with Nubeqa was maintained with long-term exposure, with a minimal increase in incidences of exposure-adjusted treatment-emergent side effects that are often linked with AR therapies. No new safety concerns were reported in ARAMIS Rollover Study.

“The ARAMIS Rollover Study extended the duration of (Nubeqa) treatment and demonstrated the long-term safety of (Nubeqa) in patients with (nonmetastatic CRPC),” lead investigator Dr. Neal D. Shore, director of Carolina Urologic Research Center, and coinvestigators, wrote in a poster presented during the meeting, held April 28 to May 1 in Chicago.

Nubeqa is a next-generation AR inhibitor with low blood–brain barrier penetration and low potential for potentially dangerous interactions with other drugs. In July 2019, the FDA approved Nubeqa for use in this patient population, based on data from the ARAMIS trial.

ARAMIS Unblinded, Patients Continue With Nubeqa

The randomized phase 3 ARAMIS trial was unblinded (meaning that patients and providers were informed of the treatment regimen being administered) following the primary analysis. Patients in both treatment arms could have open-label Nubeqa. Following completion of the study, patients who had no evidence of metastases and clinical benefit (294 patients) could continue treatment with Nubeqa on the trial.

ARAMIS results showed that Nubeqa significantly improved metastasis-free survival (time from treatment until disease spreads) by nearly two years compared with placebo and was associated with a 31% reduction in the risk of death. Additionally, the AR inhibitor showed up to 2% difference compared with placebo in side effect incidence commonly linked with Nubeqa. The treatment discontinuation rate due to side effects was 8.9% with Nubeqa and 8.7% with placebo.

In the ARAMIS Rollover study, investigators sought to report on the duration of treatment and time course profile of side effects linked with AR-directed therapy in those who received long-term Nubeqa.

At the 2023 AUA Annual Meeting, Nubeqa duration and long-term safety were described for the 954 patients who received Nubeqa from randomization along with follow-up across the ARAMIS double-blind, open-label and rollover study periods.

In the double-blind treatment period, patients with nonmetastatic CRPC with a PSA doubling time (DT) up to 10 months (1,509 patients) were randomly assigned to receive Nubeqa at 600 mg twice daily plus androgen deprivation therapy (ADT; 955 patients) or placebo twice daily plus ADT (554 patients).

Following unblinding, and in the open-label treatment period, patients on Nubeqa continued treatment with the AR inhibitor (591 patients) and those on placebo crossed over to receive Nubeqa (170 patients). Subsequently, 294 patients migrated onto the ARAMIS Rollover portion of the research.

Stratification factors included PSA doubling time (six months or shorter vs more than six months), and whether bone-targeted therapy was received to prevent skeletal complications or not.

Results showed that Nubeqa’s clinical benefit and safety profile were maintained for several years in select patients with nonmetastatic CRPC.

In the patients randomized to receive Nubeqa, the median treatment duration in the double-blind period was 1.5 years (range, 0.0-4.0), 2.1 years (range, 0.0-4.9) in the double-blind plus open-label periods and 2.8 years (range, 0.0-6.8) in the double-blind plus open-label plus Rollover study periods.

Additional data showed that 37.6% of patients received the AR inhibitor for up to two years, 32.3% were on treatment between two and four years, 17.3% received it for four to five years and 12.8% were on Nubeqa for at least five years.

Manageable Side Effects

Regarding safety, the incidence of side effects that are often liked with AR inhibitors proved to be low with the prolonged Nubeqa treatment, with slight increases observed across the double-blind plus open-label plus rollover study periods. Furthermore, most of these effects occurred during the first two years of Nubeqa treatment.

Any-grade side effects were 85.7% in the double-blind period, 89.8% in the double-blind plus open-label period, and 91.5% in the double-blind plus open-label plus rollover study periods.

Moderate to severe (grade 3/4) side effects occurred in 26.3%, 31.8% and 35.5%, respectively. Side effects that led to treatment discontinuation occurred in 8.9%, 10.5% and 12.9% of those in the double-blind, double-blind plus open-label and double-blind plus open-label plus rollover study periods, respectively.

In the double-blind period, reported side effects often linked with AR inhibitors included fatigue (incidence rate, 13.2%), fracture (5.5%), fall (5.2%), rash (3.1%), mental impairment disorder (2%) and hypertension (7.8%).

In the double-blind plus open-label periods, the incidence rates were for 14.3% for fatigue, 8.3% for fracture, 6.9% for fall, 3.8% for rash, 2.3% for mental impairment disorder and 9% for hypertension.

Finally, these rates were reported in the double-blind plus open-label plus rollover study periods for fatigue (14.9%), fracture (9.3%), fall (8%), rash (4.1%), mental impairment disorder (3%) and hypertension (10.3%).

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