Avelumab Shows Promising Results in Advanced Urothelial Carcinoma

A phase Ib study found the anti–programmed death ligand 1 (PD-L1) antibody avelumab was well tolerated and had promising antitumor activity in patients with refractory metastatic urothelial carcinoma.

“The rationale for assessing immune checkpoint inhibitors in advanced urothelial cancer is supported by a high prevalence of tumor somatic mutations, which may generate neoantigens that are recognized by activated antitumor T cells,” wrote study authors led by Andrea B. Apolo, MD, of the genitourinary malignancies branch at the National Cancer Institute in Bethesda, Maryland.

This study was a multicenter expansion cohort trial that included 44 patients with urothelial carcinoma who progressed after platinum-based chemotherapy; patients were unselected for PD-L1 expression, and they received 10 mg/kg intravenous avelumab every 2 weeks. The results were published in the Journal of Clinical Oncology.

Patients were followed for a median of 16.5 months. All patients experienced at least one adverse event (AE); 29 patients (65.9%) had a treatment-related AE, the most common of which were fatigue (20.5%), infusion-related reaction (20.5%), and asthenia (11.4%). There were four grade 3/4 treatment-related AEs in three patients; these included elevated blood creatine phosphokinase and aspartate aminotransferase, asthenia, and decreased appetite. Nineteen patients (43.2%) had a serious AE, two of which were treatment-related. There were no treatment-related deaths.

Avelumab yielded a confirmed objective response rate of 18.2%, and a disease control rate of 52.3%. There were five patients with a complete response (11.4%), three with a partial response (6.8%), and 15 had stable disease (34.1%). Of the eight responders, five had visceral (non–lymph node) metastases.

In patients with a confirmed response, the median time to response was 13.0 weeks, and the median duration response had not been reached. Six of the eight responders had an ongoing response at the time of data cutoff. Thirteen of the patients in the study (29.5%) had a reduction in target lesions by at least 30% over baseline.

A total of 37 patients were evaluable for PD-L1 expression. Responses in these patients occurred with both PD-L1–positive and –negative tumors, though there was a trend toward higher response rates and better survival outcomes in those with PD-L1–positive tumors. The authors noted that responses were observed in patients with factors associated with poor prognosis.

The median progression-free survival was 11.6 weeks, and 19.1% of patients were progression free at 48 weeks. The median overall survival was 13.7 months; at 12 months, the overall survival rate was 54.3%.

“Findings from this study suggest that avelumab could become a potential treatment option for patients with advanced urothelial carcinoma,” the authors concluded. Other trials in this setting are ongoing.