Avelumab Maintenance Therapy for Metastatic Urothelial Cancer

Initial management of patients with metastatic urothelial cancer has, for decades, been cisplatin or carboplatin-based chemotherapy. However, most patients have disease progression within 9 months, and median overall survival (OS) is 14 to 15 months with cisplatin-based therapy and 9 to 10 months with carboplatin-based therapy.

To determine whether maintenance therapy with the anti–PD-L1 antibody avelumab would improve OS in this setting, investigators conducted an industry-sponsored, international, phase III trial involving 700 patients (median age, 68–69 years; 56%–58% PD-L1–positive) with advanced or metastatic urothelial cancer without disease progression after first-line therapy with a cisplatin or carboplatin-based regimen. Patients were randomized to receive avelumab plus best supportive care (BSC) or BSC alone.

Results at a median follow-up >19 months were as follows:

• OS (the primary endpoint) at 1 year was improved with avelumab versus BSC alone (71.3% vs. 58.4%), and median OS was 21.4 months with avelumab versus 14.3 months with BSC alone (hazard ratio for death, 0.69; P=0.001).

• OS at 1 year was also improved with avelumab versus BSC alone in PD-L1–positive patients (79.1% vs. 60.4%; HR, 0.56; P<0.001).

• Toxicity was as anticipated from a checkpoint inhibitor; the incidence of grade 3 or higher adverse events was greater with avelumab than with BSC alone (47.4% vs. 25.2%).