Darolutamide (Nubeqa) Gets OK in Europe for Prostate Cancer

Zosia Chustecka

January 31, 2020

A new drug for use in the treatment of prostate cancer is likely to be available soon in Europe ― the androgen receptor inhibitor darolutamide (Nubeqa, Bayer).

The drug received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) at its January 30 meeting, which means it has been recommended for approval. An approval from the European Medicines Agency usually follows within 67 days.

Darolutamide is intended for use in the treatment of patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease. The CHMP noted that in this patient population, the drug has been shown to delay metastatic disease. The main side effect that has been reported is fatigue, the CHMP added.

The drug was approved for a similar indication in July 2019 by the US Food and Drug Administration (FDA).

That FDA approval was based on results from the phase 3 ARAMIS trial (n = 1509), which showed a significant improvement in the primary endpoint of metastasis-free survival (MFS).

The ARAMIS trial results were presented in February 2019 at the Genitouirinary Cancers Symposium and were published online in the New England Journal of Medicine, as reported at the time by Medscape Medical News.

Until last year, no drugs had been approved for use in nmCRPC.

Now there are three — darlutamide joins two other antiandrogen products that have been approved for this indication, also on the basis of improved MFS. The other two are apalutamide (Erleada, Janssen), which was evaluated in the SPARTAN trial, and enzalutamide (Xtandi, Astellas/Pfizer), which was assessed in the PROSPER trial.

MFS is determined on the basis of independent central review of radiographic imaging every 16 weeks.

It is defined as the time from randomization to the time of first evidence of blinded, independent central review–confirmed distant metastasis or death from any cause within 33 weeks after the last evaluable scan, whichever occurs first.

It is a relatively new endpoint in prostate cancer trials, introduced in the past few years. It can be measured more quickly than the ultimate endpoint — overall survival — which can require years of follow-up. However, questions have been raised about the relevance and applicability of this surrogate endpoint.

Approached for comment earlier this year, Bobby Liaw, MD, clinical director of genitourinary oncology at Mount Sinai Health System in New York City, said that the ARAMIS trial with darolutamide showcases the activity and efficacy of a new oral androgen receptor antagonist in delaying the development of radiographically evident metastatic disease in men with nmCRPC.

"Prolonging delay in the development of metastatic disease is an endpoint that has more recently been recognized as an objective and clinically meaningful measure," he told Medscape Medical News.

Applications Withdrawn for Two Cancer Drugs

The CHMP also noted that applications for two drugs intended for use in cancer patients have been withdrawn.

One is an application for initial marketing authorization for enasidenib (Idhifa, Celgene), which had been intended for the treatment of acute myeloid leukemia. The agency had questions about the efficacy of the drug. The company stated that it could not fully address the major objections that the agency had raised and hence decided to withdraw the application.

The other was an application to extend the use of the immunotherapy pembrolizumab (Keytruda, Merck & Co) for treatment of cancer of the esophagus. In reviewing the application, the agency noted that the results from the study that had been submitted did not show that pembrolizumab was effective at prolonging the lives of patients with cancer of the esophagus. The company withdrew the application, saying that the results of the study were not considered sufficient to support an extension of indications at this time.

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