Skip to main content
          Skip to FDA Search
          Skip to in this section menu
          Skip to footer links


U.S. flagAn official website of the United States government

					Here’s how you know
          			Dot gov**The .gov means it’s official.**Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you're on a federal government site.
							      SSL**The site is secure.** The **https://** ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. 
			U.S. Food and Drug Administration
				
        Search
            Menu
							
						Search FDA
									
									Submit search 
		Featured
							Contact FDA
	                FDA Guidance Documents
	                Recalls, Market Withdrawals and Safety Alerts
	                Press Announcements
	                Warning Letters
	                Advisory Committees
	                En Español

					Products
            Food
							Drugs
							Medical Devices
							Radiation-Emitting Products
							Vaccines, Blood, and Biologics
							Animal and Veterinary
							Cosmetics
							Tobacco ProductsTopics
            About FDA
							Combination Products
							Regulatory Information
							Safety
							Emergency Preparedness
							International Programs
							News and Events
							Training and Continuing Education
							Inspections and Compliance
							Science and ResearchInformation For
            Consumers
	            Patients
	            Industry
	            Health Professionals
	            Federal, State and Local Officials 
 In this section:

                Resources for Information | Approved Drugs

Resources for Information | Approved Drugs

                        Oncology (Cancer) / Hematologic Malignancies Approval Notifications
          Ongoing | Cancer Accelerated Approvals
          Verified Clinical Benefit | Cancer Accelerated Approvals
          Withdrawn | Cancer Accelerated Approvals
          Other | Cancer Accelerated Approvals


                        Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) Short Description Home
          Drugs
          Development & Approval Process | Drugs
          Drug Approvals and Databases
          Resources for Information | Approved Drugs
          FDA D.I.S.C.O.: A new drug approval for non-metastatic castration-resistant prostate cancerResources for Information | Approved Drugs FDA D.I.S.C.O.: A new drug approval for non-metastatic castration-resistant prostate cancer
  
  	
    Share
    Post
    Linkedin

    Email
    PrintPodcast Apalutamide

FDA medical oncologists discuss the February 14, 2018, approval of apalutamide for the treatment of non-metastatic castration-resistant prostate cancer.

Dr. Sanjeeve Bala: Welcome back to the DISCO, the FDA’s Soundcast in Clinical Oncology from the Oncology Center of Excellence. We are located in Silver Spring, Maryland, and during our soundcasts, we discuss recent FDA approvals of cancer drugs and therapies. We hope this information will help you in better understanding these approvals and how new drugs and therapies are benefitting cancer patients.

I’m Dr. Sanjeeve Bala, a medical oncologist and acting clinical team leader at FDA, and I’m joined by my colleague Dr. Abhi Nair, also a medical oncologist at the Oncology Center of Excellence.

Dr. Abhi Nair: Hi everyone. Thanks for joining us.

SB: Today we will discuss apalutamide, approved in February 2018, and marketed as ERLEADA, at a recommended dose of 240 mg orally once daily. Apalutamide is a new androgen receptor antagonist for patients with non-metastatic castration-resistant prostate cancer. Until now, there were no FDA-approved treatments for patients facing this clinical situation. Abhi will explain a little on the background of localized prostate cancer before we delve into the data.

AN: Thanks, Sanjeeve. Therapy for localized prostate cancer, including surgery or radiation, can be curative. Following definitive therapy, for patients who develop rising prostate specific antigen—or PSA—levels, after definitive therapy, standard management is the suppression of testosterone by treatment with gonadotropin-releasing hormone analogs or orchiectomy.

Unfortunately, many patients may develop castration-resistant disease, with rising PSA despite these measures, which can occur in the absence of systemic metastasis. We consider this is a sort of pre-metastatic state, termed non-metastatic castration-resistant prostate cancer. Apalutamide is for these types of patients.

AN: Sanjeeve, tell us more about apalutamide.

SB: Apalutamide is an androgen receptor antagonist. In the castrate-resistant prostate cancer setting, that is, with no detectable testosterone, persistent androgen signaling can occur through a variety of mechanisms. Activation of the receptor in this setting ultimately leads to the expression of genes that promote prostate cancer growth. It’s this gene expression that apalutamide can inhibit, reducing the strength of that growth signal.

AN: Alright, time to dig into the data. Let’s hear about the trial that led to approval.

SB: Apalutamide was approved based on the SPARTAN trial, which randomized 1,207 patients with non-metastatic castration-resistant prostate cancer 2:1 to treatment with either apalutamide 240 mg once daily or placebo. All patients also had androgen deprivation, defined as medical or surgical castration.

AN: So these were patients who had definitive treatment for localized prostate cancer and androgen deprivation for rising PSA in the absence of identifiable metastasis. Tell us a bit more about the trial endpoints and results.

SB: The major efficacy endpoint was metastasis-free survival, or MFS. MFS was defined as the time from randomization to the time of first evidence of distant metastasis or death.

AN: And let me add that metastasis was defined as new bone or soft tissue lesions or enlarged lymph nodes outside the pelvis. So what did the trial demonstrate?

SB: The estimated median metastasis-free survival was 40.5 months for the patients treated with apalutamide, vs. 16.2 months for those receiving the placebo.

AN: That’s a pretty big difference, and understandably apalutamide received regular approval for these results. Let’s now go over the safety signals.

SB: In the clinical trial, falls occurred in 16% of patients on the apalutamide arm vs 9% on placebo, and fractures occurred in 12% on the apalutamide arm and 7% on placebo, although routine bone densitometry wasn’t performed in this study. Also, seizures occurred in two of the 806 patients on the apalutamide arm, and the prescribing information contains a warning to discontinue apalutamide in any patient who develops a seizure during treatment. Detailed safety information is available in the product label as always.

AN: Great. I think the metastasis-free survival endpoint used in this approval is promising, because it represents a new way of measuring clinical benefit in these patients, and also opens a new regulatory pathway for drug approval. Sanjeeve, let’s sum up with the three take-away points for our listeners.

SB: Sure, the three main take away points are: 1) apalutamide is the first antiandrogen approved for the treatment of men with non-metastatic castration resistant prostate cancer; 2) the approved dose is 240 mg orally once daily; and 3) falls and seizures are some of the important safety concerns when treating men with apalutamide.

SB: You can find more details in the prescribing information, which is also online at Drugs@FDA. For a transcript with a link to the prescribing information and the multidisciplinary team of FDA experts who conducted the review, visit the FDA Oncology Center of Excellence DISCO website at fda.gov/DISCO.

AN: And so, to our listeners, are there other FDA oncology drug approvals that you would like to hear about? Leave us your questions and comments on Twitter @FDAOncology and as always, we welcome your feedback at our email address, FDAoncology@fda.hhs.gov. I’m Abhi Nair, thank you for tuning in to DISCO today.

SB: And until next time at the DISCO, I’m Sanjeeve Bala.

Acknowledgements:

This Drug Information Soundcast in Clinical Oncology was developed by Abhilasha Nair, Sanjeeve Bala, Marc Neilson, Dow-Chung Chi, Daniel L. Suzman, Kirsten B. Goldberg, and Richard Pazdur, of the Oncology Center of Excellence and the Office of Hematology and Oncology Products. Steven Jackson of the Division of Drug Information was the sound producer.

Reviewers for this New Drug Application were:

Regulatory Project Manager: Charlene Wheeler
Nonclinical: Wei Chen, Todd Palmby
Clinical Pharmacology: Wentao Fu, Qi Liu
Clinical: Dow-Chung Chi, Daniel L. Suzman, Chana Weinstock
Statistical: Lijun Zhang, Jason Schroeder
Labeling: William Pierce
Cross-Disciplinary Team Leader: Chana Weinstock
Division Director (DHOT) John Leighton
Division Director (OCP) NAM Atiqur Rahman
Division Director (OB) Rajeshwari Sridhara
Division Director (OHOP/DOP1) Julia Beaver
Office Director (designated signatory): Gideon Blumenthal

                                                                                  Content current as of:
      05/07/2018
              
              
Regulated Product(s)
		 Drugs
			  			     			  						              
			
			
			
			
						  OncologyResources for Information | Approved Drugs

          
                        Oncology (Cancer) / Hematologic Malignancies Approval Notifications
          Ongoing | Cancer Accelerated Approvals
          Verified Clinical Benefit | Cancer Accelerated Approvals
          Withdrawn | Cancer Accelerated Approvals
          Other | Cancer Accelerated Approvals


                        Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) Short Description
 
 Footer Links
    FDA Archive
          About FDA
          Accessibility
      Visitor Information
          Website Policies / Privacy
          No FEAR Act
          Vulnerability Disclosure Policy
      FOIA
          HHS.gov
          USA.gov
    Contact FDA
      Follow FDA on Facebook
      Follow FDA on X
      Follow FDA on Instagram
      Follow FDA on LinkedIn
      View FDA videos on YouTube
      Subscribe to FDA RSS feeds
    FDA Homepage
    Contact Number
      1-888-INFO-FDA (1-888-463-6332) Back toTop