Apalutamide (ARN-509) Approved to Treat Non-Metastatic, Hormone-Resistant Prostate Cancer

On Feb. 14th, the U.S. Food and Drug Administration approved apalutamide (Erleada®, previously  called ARN-509) for the treatment of non-metastatic, castration (hormone)-resistant prostate cancer (CRPC). Apalutamide could be administered in a clinical setting wherein men who are being treated with androgen (hormone) deprivation therapy (ADT) see their PSA levels begin to rise, but no metastases are visible yet on bone or CT scans. There were previously no FDA-approved treatments for non-metastatic CRPC, and patients typically continued to receive ADT, despite its diminishing benefit.

This FDA approval was based on results from a randomized phase 3 SPARTAN clinical trial presented at the February 2018 ASCO Genitourinary Cancers Symposium. The SPARTAN trial tested apalutamide versus placebo and whatever treatment the men were already given (mostly ADT), in 1,207 non-metastatic CRPC patients with rapidly rising PSA levels of doubling time 10 months or less. Patients selected for the trial had no distant metastases based on bone and computed tomography (CT) scans of the pelvis, abdomen, chest and head. Some patients had malignant local or regional (pelvic) lymph nodes no larger than  2 cm on the short axis.

Apalutamide was found to delay the time to metastatic disease by over 24 months on average (40.5 months in the apalutamide group vs. 16.2 months in the placebo group). This represents a 72% reduction in risk of metastasis or death. The full results have been published in the New England Journal of Medicine.

This website recently contained a blog on ARN-509 and the SPARTAN trial posted on November 10th, 2017. The similarities between apalutamide (ARN-509) and enzalutamide were noted.  Their chemical structures are indeed very similar. They differ only in two areas of the molecule where chemists who develop drugs would anticipate making changes. Enzalutamide contains a 5-membered heterocyclic ring with a carbon-sulfur double bond whereas apalutamide contains a carbon-oxygen double bond (carbonyl) in its place. In addition, enzalutamide contains a dimethyl group on heterocyclic ring whereas this is replaced by a fused cyclobutyl ring in apalutamide. Further comparisons and similarities will be noted in future posts.


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