FDA Approves Nubeqa in Metastatic Castration-Sensitive Prostate Cancer

The FDA approved Nubeqa for metastatic castration-sensitive prostate cancer based on significantly improved radiographic progression-free survival data.

The United States Food and Drug Administration (FDA) approved Nubeqa (darolutamide) for the treatment of metastatic castration-sensitive prostate cancer, according to a news release from the FDA.

Nubeqa significantly improved radiographic progression-free survival (rPFS) compared with placebo. Median rPFS was not reached in the Nubeqa arm and was 25 months in the placebo arm. There was no statistically significant difference in overall survival at the time of the final analysis.

Side effects in the Nubeqa group were consistent with previous experience with the drug as a single agent. The prescribing information includes warnings for ischemic heart disease, seizure and embryo-fetal toxicity.

The randomized phase 3 ARANOTE trial evaluated the efficacy and safety of Nubeqa (darolutamide) versus placebo in 669 patients with metastatic castration-sensitive prostate cancer. All patients also received a gonadotropin-releasing hormone analog or had previously undergone bilateral orchiectomy.

rPFS served as the primary end point of the study, assessed by blinded independent central review. Overall survival (OS) was a secondary endpoint.

The recommended dose of Nubeqa is 600 milligrams — two 300 milligram tablets — taken orally, twice daily, with food until disease progression or unacceptable toxicity.

The ARANOTE trial enrolled adults 18 or older with confirmed metastatic prostate adenocarcinoma based on imaging and pathology. Participants had to have an ECOG performance status between 0 and 2 and adequate liver, kidney and bone marrow function.

All patients began androgen deprivation therapy (ADT) within 12 weeks before starting the study. They were randomly assigned in a 2-to-1 ratio to receive either 600 milligrams of darolutamide twice daily or a matched placebo. Stratification was based on prior local treatment and the presence of visceral metastases.

Additional Efficacy Data

At the 50th Annual Oncology Nursing Society Congress, nurses were presented with updated safety and efficacy findings from the phase 3 ARANOTE study to help guide patient education and support. The data, previously shared in a poster presentation, showed that combining Nubeqa with ADT reduced the risk of radiological progression or death by 46% compared with ADT alone. Median rPFS was not reached in the Nubeqa group versus 25 months in the control group. At 24 months, 70.3% of patients receiving Nubeqa remained progression-free, compared with 52.1% of those on ADT alone.

A favorable trend in overall survival was also noted, with the Nubeqa combination reducing the risk of death by 19%. Additionally, the risk of progressing to metastatic castration-resistant prostate cancer was reduced by 60%, with the median time to progression not reached in the Nubeqa arm versus 13.8 months in the control arm.

Previous 2022 FDA Approval

Previously, on August 5, 2022, the FDA approved Nubeqa in combination with docetaxel for adults with metastatic hormone-sensitive prostate cancer.

In the ARASENS trial, which enrolled 1,306 patients, adding Nubeqa to docetaxel significantly improved overall survival compared with docetaxel and placebo. Median overall survival was not reached in the Nubeqa arm versus 48.9 months with placebo. Time-to-pain progression was also significantly delayed with the addition of Nubeqa.

The most common side effects in patients receiving Nubeqa plus docetaxel — occurring in at least 10% of patients with a 2% or greater increase over placebo — were constipation, decreased appetite, rash, hemorrhage, weight gain, and hypertension. Laboratory abnormalities in at least 30% of patients included anemia, hyperglycemia, low lymphocyte and neutrophil counts, elevated AST and ALT, and low calcium levels.

Patients in ARASENS had a median age of 67, with 17% aged 75 or older. The trial included a diverse population: 52% were White, 36% Asian, 4% Black or African American, and 7% Hispanic or Latino. Most had M1b disease (bone metastases), with smaller proportions having M1a (distant lymph nodes) or M1c (organ involvement). All participants received a gonadotropin-releasing hormone analog or had a bilateral orchiectomy.

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