The PD-L1 inhibitor has been recommended for approval in this setting based on data from the phase 3 JAVELIN Bladder 100 study.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of the PD-L1 inhibitor avelumab (Bavencio) for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.1
The recommendation was based on data from the phase 3 JAVELIN Bladder 100 study, in which the median overall survival (OS) was 21.4 months with avelumab plus best supportive care (BSC) compared with 14.3 months with BSC alone.2 This 7.1-month benefit translated to a 31% reduction in the risk of death (HR, 0.69; 95% CI, 0.56-0.86; P <.001).
The CHMP’s recommendation will now be reviewed by the European Commission, with a final decision anticipated by early next year.
"Patients living with locally advanced or metastatic urothelial carcinoma in Europe are in urgent need of more treatment options that have the potential to extend their lives," Chris Boshoff, MD, PhD, chief development officer, Oncology, Pfizer Global Product Development, which codevelops avelumab with EMD Serono (Merck KGaA), stated in a press release. "The overall survival results from JAVELIN Bladder 100 show the potential benefits of a first-line maintenance approach with Bavencio as a significant advancement for patients with locally advanced or metastatic urothelial carcinoma."
The open-label, international JAVELIN Bladder 100 trial included 700 patients with locally advanced or metastatic urothelial cancer who achieved a complete response (CR), partial response (PR), or stable disease (SD) after receiving 4 to 6 cycles of standard gemcitabine combined with either cisplatin or carboplatin.
Patients were randomized in a 1:1 ratio to intravenous avelumab (10 mg/kg every 2 weeks in 4-week cycles) plus BSC or BSC alone. Specific components of BSC could be correction of metabolic disorders, antibiotics, pain management, nutritional support, and symptom control.
The primary end point was OS, with key secondary end points including progression-free survival and safety.
The investigators reported that the avelumab OS benefit was observed across patient subgroups, including those defined by best response to treatment (CR, PR, or SD), and choice of frontline platinum chemotherapy (carboplatin or cisplatin).
Biomarker testing showed that 51% (n = 358) of patients were PD-L1 positive across the overall study population. In this subgroup, avelumab plus BSC induced a 44% reduction in the risk of death compared with BSC alone (HR, 0.56; 95% CI, 0.40-0.79; P <.001). An exploratory analysis was also conducted among PD-L1–negative patients (n = 271), showing a hazard ratio for OS of 0.85 (95% CI, 0.62-1.18).
Adverse events (AEs) across all grades occurred in 98% versus 77.7% of the avelumab and control groups, respectively. Grade 3 AEs occurred in 47.4% versus 25.2% of the 2 arms, respectively.
The FDA approved avelumab in July 2020 for use in this setting.
1. BAVENCIO® (avelumab) Receives Positive CHMP Opinion for First-Line Maintenance Treatment of Locally Advanced or Metastatic Urothelial Carcinoma. Posted online December 11, 2020. https://prn.to/37fpKSY. Accessed December 14, 2020.
2. FDA Approves BAVENCIO as First-Line Maintenance Treatment for Patients with Locally Advanced or Metastatic Urothelial Carcinoma. Posted June 30, 2020. https://prn.to/2ZvnzFA. Accessed June 30, 2020.