Avelumab in Refractory Metastatic Urothelial Carcinoma


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The programmed cell death ligand 1 (PD-L1)–inhibitor avelumab (Bavencio) has shown activity in patients with refractory metastatic urothelial cancer, according to findings in a phase Ib study reported by Andrea B. Apolo, MD, of the Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, and colleagues in the Journal of Clinical Oncology. This patient cohort is part of the ongoing JAVELIN Solid Tumor study investigating the activity of avelumab in metastatic or locally advanced solid tumors, with expansion in selected tumor types.

Andrea B. Apolo, MD

Andrea B. Apolo, MD

The multicenter expansion cohort study included treatment of 44 patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression with avelumab at 10 mg/kg intravenously every 2 weeks. PD-L1 positivity was defined as expression on ≥ 5% of tumor cells on immunohistochemistry. In total, 54% of patients had received ≥ 2 previous lines of therapy for advanced disease, and 30% had PD-L1 expression ≥ 5% on tumor cells.

Response Rates

Median follow-up was 16.5 months. Confirmed objective response on independent central review was achieved in 8 patients (18.2%, 95% confidence interval [CI] = 8.2%–32.7%), including a complete response in 5 patients. An additional 15 patients (34.1%) had stable disease, yielding a disease control rate of 52.3%. Median duration of response was not reached (95% CI = 12.1 weeks to not estimable); responses were ongoing at data cutoff in six responders, including four of five with a complete response. Of eight responding patients, seven had PD-L1–positive tumors. The confirmed objective response rate was 53.8% in PD-L1–positive tumors (7 of 13 patients) and 4.2% in PD-L1–negative tumors (< 5% expression, 1 of 24 patients).

Overall, median progression-free survival was 11.6 weeks (95% CI = 6.1–17.4 weeks). Median overall survival was 13.7 months (95% CI = 8.5 months to not estimable), with 12-month overall survival of 54.3%.

Adverse Events

The most common treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Serious adverse events occurred in 19 patients (43.2%) and were considered treatment-related in 2 (elevated creatine phosphokinase and aspartate transaminase in 1 patient, asthenia in 1 patient). Avelumab was permanently discontinued in four patients (9.1%) due to a treatment-related adverse event. A treatment-related adverse event of any grade that was considered potentially immune-related occurred in nine patients (20.5%).

The authors concluded: “Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic [urothelial carcinoma].”

They continued: “On the basis of the promising clinical activity seen in this cohort of the JAVELIN Solid Tumor trial, an additional expansion cohort of approximately 200 patients with urothelial carcinoma has been enrolled to further characterize the efficacy and safety of avelumab in this patient population. In addition, a randomized phase III trial of avelumab plus best supportive care versus best supportive care alone as maintenance therapy in patients with metastatic urothelial carcinoma not progressing after first-line platinum-based therapy is underway.” ■

Apolo AB, et al: J Clin Oncol 35:2117-2124, 2017.


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