FDA Approves Urothelial Carcinoma Maintenance Treatment

The U.S. Food and Drug Administration (FDA) approved avelumab (BAVENCIO, EMD Serono) for maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy.

Efficacy of avelumab for maintenance treatment of UC was investigated in the JAVELIN Bladder 100 trial (NCT02603432), a randomized, multi-center, open-label trial that enrolled 700 patients with unresectable, locally advanced or metastatic urothelial carcinoma that had not progressed with four to six cycles of first-line platinum-containing chemotherapy. Patients were randomized (1:1) to receive either avelumab intravenously every 2 weeks plus best supportive care (BSC) or BSC alone. Treatment was initiated within 4-10 weeks after last chemotherapy dose.

The main efficacy outcome measures were overall survival (OS) in all patients and in patients with PD-L1-positive tumors. The median OS in all patients was 21.4 months in the avelumab arm and 14.3 months in the BSC alone arm (HR: 0.69; 95%CI: 0.56, 0.86; p=0.001). Among patients with PD-L1-positive tumors (51%), the HR for OS was 0.56 (95% CI: 0.40, 0.79; p<0.001). In an exploratory analysis of patients with PD- L1- negative tumors (39%), the OS hazard ratio was 0.85 (95% CI: 0.62, 1.18).

The most common adverse reactions in > 20% of patients who received avelumab were fatigue, musculoskeletal pain, urinary tract infection, and rash. One patient died from sepsis and 28% of patients had serious adverse reactions.

The recommended avelumab dose is 800 mg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.

The results from this study supported the conversion of accelerated approval of avelumab to a regular approval.