FDA Grants Accelerated Approval to Avelumab for Urothelial Carcinoma

Approval was based on data from an open-label, single arm, multi-center study that enrolled 242 patients with locally advanced or metastatic urothelial carcinoma whose disease progressed on or after platinum-based therapy or within 12 months of a platinum-containing neoadjuvant or adjuvant chemotherapy regimen. Patients received avelumab, 10 mg/kg via IV, every two weeks until radiographic or clinical progression or unacceptable toxicity. All patients received premedication with an antihistamine and acetaminophen prior to each avelumab administration. Confirmed overall response rate (ORR) in patients who had been followed for at least 13 weeks was 13.3% (n = 30) (95% CI = 9.1, 18.4), and 16.1% (n = 26) (95% CI = 10.8, 22.8) in patients who had been followed for at least 6 months. Median time to response was 2.0 months (range = 1.3-11.0). The median response duration had not been reached in patients followed for at least 13 weeks or at least six months, but ranged from 1.4+ to 17.4+ months in both groups.

Deaths because of an adverse reaction occurred in 6% of patients. Serious adverse reactions were reported in 41% of patients. The most frequent serious adverse reactions reported in 2% or more of patients were urinary tract infection/urosepsis, abdominal pain, musculoskeletal pain, creatinine increased/renal failure, dehydration, hematuria/urinary tract hemorrhage, intestinal obstruction/small intestinal obstruction, and pyrexia. The most common adverse reactions that occurred in at least 20% of patients were fatigue, infusion-related reaction, musculoskeletal pain, nausea, decreased appetite, and urinary tract infection.

The recommended dose of avelumab is 10 mg/kg as an IV infusion over 60 minutes every two weeks. Premedicate with an antihistamine and acetaminophen prior to the first four infusions of avelumab.

Full prescribing information is available (https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761078s000lbl.pdf).

FDA granted this application priority review. FDA approved avelumab for this indication approximately three months ahead of the goal date. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics (http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf).

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online (http://www.fda.gov/medwatch/report.htm), by faxing (800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (800-FDA-1088).

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