Pooled Analysis Shows Avelumab Promising in Advanced Urothelial Carcinoma

The immune checkpoint inhibitor avelumab showed promising antitumor activity and a manageable toxicity profile in patients with platinum-refractory metastatic urothelial carcinoma, according to a new analysis.

“Antibodies targeting the programmed death ligand 1 (PD-L1) or programmed death 1 (PD-1) axis can enhance T-cell–mediated antitumor immunity by blocking inhibitory signals generated by these immune checkpoint proteins,” wrote study authors led by Manish R. Patel, MD, of the Sarah Cannon Research Institute in Sarasota, Florida. Avelumab, an anti–PD-L1 antibody, was granted accelerated approval in this setting by the US Food and Drug Administration (FDA) in May.

The new study was a planned pooled analysis of two expansion cohorts of the JAVELIN Solid Tumor trial, extending the follow-up beyond what was used in the FDA approval. It included 249 patients who had progressed after at least one previous platinum-based chemotherapy regimen, followed for a median of 9.9 months; 161 of those patients had at least 6 months of follow-up and were included in the efficacy analysis. Results were published in Lancet Oncology.

All patients had advanced metastatic urothelial carcinoma. The median age of patients was 68 years, 72% were male, and 78% were white. Using a ≥ 5% cutoff, 33% of the cohort was PD-L1–positive.

Among the 161 eligible patients, there were 27 (17%) with a response to avelumab. Nine patients had a complete response (6%), and 18 had partial responses (11%); another 37 patients (23%) had stable disease. The overall disease control rate was 40%.

In patients who were PD-L1–positive, the disease control rate was 52%, and 24% had a confirmed response including 10% with a complete response. Only 13% of PD-L1–negative patients had a confirmed response, and the disease control rate in these patients was 33%.

In the full cohort, 58% of patients had any grade 1/2 adverse event, 7% had a grade 3 event, 1% had a grade 4 event, and there was one grade 5 event (pneumonitis). The most common event was infusion-related reaction, which occurred at grade 1/2 in 29% of patients. Among the other most common adverse events were fatigue, rash, diarrhea, and asthenia.

“Durable and complete responses following first-line chemotherapy in patients with metastatic urothelial carcinoma are rare,” the authors wrote. The encouraging activity seen with avelumab has led to an ongoing phase III trial assessing avelumab as maintenance therapy compared with best supportive care in patients with metastatic disease who have not progressed after first-line chemotherapy with a platinum-based regimen.

“Overall, our findings suggest that avelumab is generally well tolerated and shows promising antitumor activity in patients with platinum-refractory metastatic urothelial carcinoma,” they concluded.