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          Withdrawn | Cancer Accelerated Approvals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.: Avelumab in Merkel Cell Carcinoma TranscriptResources for Information | Approved Drugs FDA D.I.S.C.O.: Avelumab in Merkel Cell Carcinoma Transcript
  
  	
    Share
    Post
    Linkedin

    Email
    PrintPodcast
*FDA medical oncologists discuss the agency’s March 23, 2017, approval of avelumab the treatment of patients 12 years and older with metastatic Merkel cell carcinoma.*
*Transcript:*
Sanjeeve Bala: Once again, welcome to the D.I.S.C.O. Today’s Drug Information Soundcast in Clinical Oncology from FDA’s Oncology Center of Excellence will focus on the recent approval of avelumab, marketed as Bavencio.
Abhi Nair: The world of immuno-oncology has changed the landscape for many cancers like melanoma. But for rare skin cancers such as Merkel cell carcinoma, there have been no FDA approved drugs until avelumab. So it was a pivotal moment for patients with metastatic Merkel cell carcinoma when FDA approved the first treatment for this rare but life-threatening disease.
AN: Hi, I’m Abhilasha Nair, a medical oncologist at the Oncology Center of Excellence at the FDA.
SB: And I’m Sanjeeve Bala, a medical oncologist and clinical team leader.
AN: I’m really excited to be here at the D.I.S.C.O. today since we’re going to discuss a landmark approval for patients with metastatic Merkel Cell Carcinoma.
SB: I agree Abhi. Merkel cell carcinoma is a rare, aggressive neuroendocrine tumor of the skin. Prior to the approval of avelumab, there were no FDA approved treatments for patients with metastatic disease. While the vast majority of cases are initially amenable to surgical resection, the recurrence rate is high, with more than a third of patients eventually developing metastatic disease.
AN: Sanjeeve, what was considered standard of care for these patients in the advanced setting prior to the approval of avelumab?
SB: The most common drugs used to treat this disease are cisplatin or carboplatin in combination with etoposide or single agent topotecan. Patients usually get platinum-based chemotherapy, but responses to chemotherapy are not generally durable, such that an improvement in overall survival has not been demonstrated. Most patients are older adults over 70, and especially for this population, these standard regimens can be challenging, causing serious and sometimes fatal adverse reactions. So the avelumab approval is a major advance in this disease.
AN: Before we get too far, give us a little background on avelumab.
SB: Avelumab is a monoclonal antibody directed against programed death ligand 1 (or PD-L1), which shares a mechanism of action with a few other recent immuno-oncology approvals.
AN: And the indication for this approval?
SB: It is approved for the treatment of adults and pediatric patients 12 years and older who have metastatic Merkel cell carcinoma.
AN: Based on what kind of data?
SB: Avelumab was granted accelerated approval based on data from an open-label, single-arm, multi-center trial (the JAVELIN Merkel 200 trial). In this trial, 88 patients with metastatic Merkel Cell tumors, previously treated with one line of chemotherapy, were treated with avelumab, 10 mg/kg intravenously every two weeks. They demonstrated a durable overall response rate of 33% as determined by an independent review committee. Eighty-six percent of responses were of greater than 6 months’ duration and 45% of patients maintained a response for greater than a year. This is a major improvement in response duration.
AN: I heard about some novel supportive data that were incorporated into the review. Real-world data are going prime-time?
SB: You’re right, Abhi. A retrospective, observational study—a chart review of electronic medical records obtained in community and academic centers—was submitted to describe the natural history of metastatic Merkel Cell tumor. This supportive study collected information on the outcomes of patients with metastatic Merkel Cell carcinoma treated in the first line and beyond. The data describe the relatively poor treatment outcomes following administration of cytotoxic chemotherapies.
AN: The avelumab indication covers first-line treatment, though the trial enrolled only patients who had prior chemotherapy. How did that come about?
SB: It’s another interesting feature of this approval. Treated and untreated adults with Merkel cell tumor appear to have similar disease biology. Since there’s no approved first-line chemotherapy, there is no reason to suspect that avelumab treatment would be any less efficacious in the first-line setting.
AN: Was the reasoning for including pediatric patients in the indication similar to the inclusion of previously-untreated patients?
SB: Yes. We’ve seen no significant differences in this disease and its natural history between adults and children. The extreme rarity of this disease in children makes a clinical trial of avelumab in pediatric patients infeasible. Given the very poor prognosis for adolescents with Merkel cell tumor, and the similar physiology and pharmacokinetics between adolescents and adults, the review team concluded that the benefits clearly outweighed the risks for the adolescent population.
AN: So that’s why the company must now characterize the safety and effects of avelumab in pediatric patients aged 12 years and older with solid tumors as a Post-Marketing Requirement.
AN: What were some additional regulatory considerations that the team reviewed for this application?
SB: Because of the accelerated approval pathway, a further study is required to confirm the clinical benefit of avelumab.
AN: Tell us about the safety risks of avelumab? Is it similar to other PD-1 inhibitors?
SB: The most common serious adverse reactions to avelumab were immune-mediated adverse reactions such as pneumonitis, colitis, and hepatitis. This is expected for this drug class. However, there was an increased incidence of infusion-related reactions with life threatening infusion reactions observed in 0.2% of patients. These occurred mostly within the first two cycles of treatment, and are not as common for other agents in this class.
SB: The product label recommends that all patients receive premedication with an antihistamine and acetaminophen prior to the first four infusions of avelumab. Serious adverse reactions that occurred in more than one patient in the pivotal trial were acute kidney injury, anemia, abdominal pain, ileus, fatigue, and cellulitis. Detailed safety information is available in the product label.
AN: Were there any subpopulations of interest with any major differences in efficacy and safety?
SB: An interesting observation was that responses were observed in patients regardless of PD-L1 tumor expression or detection of Merkel cell polyomavirus.
AN: So to conclude, Sanjeeve, what are the three take-away points from this soundcast for the listeners?
SB: Sure Abhi. The three main take-away points are: the impressive response rates, the durability of the responses observed, and the favorable safety profile of avelumab when compared to conventional chemotherapy. These are important particularly in elderly patients with this disease.
SB: Detailed information may be found in the package insert at the FDA website. For a transcript and an in-depth look at the FDA analysis and the multidisciplinary team of FDA experts who conducted the review, go to the FDA Oncology Center of Excellence website at www.fda.gov/OCE.
A: Thank you Sanjeeve. Please leave us your questions and comments on Twitter @FDAOncology. We want your feedback. Are there other FDA oncology drug approvals that you would like to hear about? Tweet us @FDAOncology. I’m Abhi Nair, and thank you for listening.
S: And until next time at the D.I.S.C.O., I’m Sanjeeve Bala.
*Acknowledgements*:
*This Drug Information Soundcast in Clinical Oncology was developed by Sanjeeve Bala, Abhilasha Nair, Denise Casey, Suzanne Demko, Patricia Keegan, 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.*
*The**FDA review documents**for this product approval are available on**Drugs@FDA**.*
*Members of the Multi-Disciplinary Review and Evaluation team for this product application were:*
Regulatory Project Manager
        Idara Udoh, M.S.Nonclinical Reviewer
        Alexander Putman, Ph.D.Nonclinical Team Leader
        Whitney Helms, Ph.D.Office of Clinical Pharmacology Reviewer(s)
        Safaa Burns, Ph.D.; Nan Zheng, Ph.D.;Office of Clinical Pharmacology Team Leader(s)
        Jeanne Fourie Zirkelbach, Ph.D.; Jiang Liu, Ph.D.Clinical Reviewer
        Denise Casey, M.D.Clinical Team Leader
        Suzanne Demko, P.A.-C.Statistical Reviewer
        Pallavi Mishra-Kalyani, Ph.D.Statistical Team Leader
        Kun He, Ph.D.Cross-Disciplinary Team Leader
        Suzanne DemkoDivision Director (DHOT)
        John Leighton, Ph.D.Division Director (OCP)
        Nam Atiqur Rahman, Ph.D.Division Director (OB)
        Rajeshwari Sridhara, Ph.D.Division Director (OHOP)
        Patricia Keegan, M.D.Office Director
        Richard Pazdur, M.D.
*Additional reviewers of the application were:*
OBP
        Team Leader: Joel Welch; Reviewer: Arulvathani ArudchandranOBP Labeling
        Jibril Abdus-SamadMicrobiology
        DS Reviewer: Maria Reyes Candau-Chacon, DP Reviewer: Lakshmi Narashmhan; QAL: Patricia HughesOPDP
        Team Leader: Trung-Hieu Tran; Reviewer: Nicholas SeniorOSI
        Team Leader: Susan Thompson: Reviewer: Lauren Iacono-ConnorOSE/DMEPA
        Team Leader: Alice Chi-Ming Tu; Reviewer: Janine StewartOSE/DRISK
        Team Leader: Doris Auth; Reviewer: Naomi ReddOther
        Anne Marie Trentacosti, Labeling Development TeamOther
        Morgan Walker, Patient Labeling (DMPP)
OBP=Office of Biotechnology Products
  
  OPDP=Office of Prescription Drug Promotion
  
  OSI=Office of Scientific Investigations

                                                                                  Content current as of:
      05/22/2017
              
              
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