FDA Grants Accelerated Approval to Avelumab for Urothelial Carcinoma

FDA granted priority review for this application for PD-L1 blocking antibody in locally advanced or metastatic urothelial carcinoma patients

On 9 May, 2017, the US Food and Drug Administration (FDA) granted accelerated approval to avelumab (BAVENCIO, EMD Serono, Inc.) for patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

Approval was based on data from an open-label, single arm, multicentre 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 intravenously, every 2 weeks until radiographic or clinical progression or unacceptable toxicity. All patients received pre-medication with an anti-histamine 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 6 months, but ranged from 1.4+ to 17.4+ months in both groups.

Deaths due to 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, haematuria/urinary tract haemorrhage, 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 intravenous infusion over 60 minutes every 2 weeks. Pre-medicate with an anti-histamine and acetaminophen prior to the first four infusions of avelumab. 

Full prescribing information is available here.  

FDA granted this application priority review. FDA approved avelumab for this indication approximately 3 months ahead of the goal date.

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.