On February 14th, the FDA approved apalutamide (Erleada™) tablets for the treatment of nonmetastatic castration resistant prostate cancer . Prostate cancer is the most common malignancy and second most common cause of cancer-related death in men in the United States . Prostate cancer cells are typically dependent on androgen receptor (AR) signaling for proliferation and survival, thus androgen deprivation therapy (ADT), or medical castration, is a standard treatment for patients with prostate cancer. Unfortunately, most prostate cancers develop resistance to ADT by evolving androgen independent AR signaling, resulting in disease progression and life-threatening metastases . Apalutamide is a small molecule that directly binds to and inhibits AR molecules, thus bypassing various castration resistance mechanisms .
The approval was based on impressive efficacy results from a large, randomized phase 3 study, SPARTAN, that compared apalutamide treatment plus standard ADT to ADT alone for the treatment of men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis . The study found that the addition of apalutamide to ADT reduced the risk of metastasis or death by 70% compared to ADT alone with a median metastasis-free survival of 40.5 months vs. 16.2 months, respectively . Apalutamide was found to be well tolerated; however, it was associated with a higher incidence of rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%) . Apalutamide has the potential to fill an unmet medical need by preventing metastasis in men with nonmetastatic castration resistant prostate cancer and paves the way for other molecules with similar mechanisms of action to be explored.
–Zachary Moore, on behalf of the Medical Content Team
- ERLEADA (apalutamide) tablets. Drugs@FDA: FDA Approved Drug Products 02/14/2018 [cited 2018 April 11]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210951s000lbl.pdf.
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- A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer (SPARTAN). ClinicalTrials.gov February 8, 2018 [cited 2018 April 11]; Available from: https://clinicaltrials.gov/ct2/show/NCT01946204.
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