JAVELIN Points To Further Avelumab Investigation For Metastatic Urothelial Carcinoma

Avelumab shows tolerability and efficacy in patients with metastatic urothelial carcinoma that has progressed after platinum-based chemotherapy

medwireNews: The anti-programmed cell death ligand (PD-L1) antibody avelumab has shown anti-tumour activity and a manageable safety profile in a phase I trial of patients with metastatic urothelial carcinoma.

Of the 249 patients who were given a 1-hour infusion of avelumab 10 mg/kg every 2 weeks, for a median of 12 weeks, all but seven patients had previously received platinum-based chemotherapy, explain Andrea Apolo, from Magnuson Clinical Center in Bethesda, Maryland, USA, and co-investigators.

The most common treatment-related events in the cohort were infusion-related reactions (29%, grade 1–2) and fatigue (16%). A further 8% of patients had grade 3 or worse adverse events, most commonly fatigue (2%); 1% of patients developed grade 3 or higher asthenia, elevated lipase, hypophosphataemia and pneumonitis.

In all, 8% of patients had a serious avelumab-related event and there was one treatment-related fatality from pneumonitis.

Furthermore, of the 161 post-platinum patients with at least 6 months of follow-up who were assessed for best overall RECIST response to avelumab, 17% achieved a complete (6%) or partial (11%) response, the team reports in The Lancet Oncology.

The disease control rate – including a complete or partial response or stable disease – was 40% and 22% of patients had a tumour reduction of at least 30% from baseline, they add.

Median time to response was 11.4 weeks and 96% of responses lasted at least 24 weeks, with median duration of response not yet reached. Median progression-free survival was 6.3 weeks and 23% of patients were free from progression at week 24; the corresponding rates for overall survival were 6.5 months and 53%.

“Given avelumab’s encouraging antitumour activity in post-platinum patients and safety profile in post-platinum and cisplatin-naive patients with metastatic urothelial carcinoma, an ongoing phase 3 trial will assess the antitumour activity of maintenance treatment with avelumab plus best supportive care compared with best supportive care alone in patients with metastatic urothelial carcinoma whose disease has not progressed after completion of first-line chemotherapy with a platinum-based regimen”, the researchers say.

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

Writing in an accompanying comment, Toni Choueiri, from Dana-Farber Cancer Institute in Boston, Massachusetts, USA, and co-authors note that the JAVELIN Solid Tumor findings have led to accelerated approval for avelumab in this indication from the US Food and Drug Administration. 

However, they note that there are now five PD-L1 and PD-1 inhibitors for platinum-refractory metastatic urothelial carcinoma available in the USA and little data to compare these options, prompting them to suggest that “the treatment choice may well hinge on frequency of delivery, the physician’s familiarity with the agent, and the level of evidence for the agent.”

Noting that second-line pembrolizumab is yet the only agent to demonstrate an overall survival benefit for advanced urothelial carcinoma, they conclude that “the therapeutic role for this particular agent [avelumab] over others in urothelial carcinoma remains unclear.”


Patel MR, Ellerton J, Infante JR, et al. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol; Advance online publication 4 December 2017.

Lalani A-KA, McGregor BA, Sonpavde GP, Choueiri TK. JAVELIN: avelumab another spear to fight urothelial carcinoma. Lancet Oncol; Advance online publication 4 December 2017.

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