Avelumab benefit may extend to cisplatin-unfit bladder cancer patients

The anti-PD-L1 antibody avelumab demonstrated clinical activity as first-line treatment for patients with metastatic or locally advanced urothelial carcinoma who were PD-L1-positive and ineligible for cisplatin, according to findings from the ARIES trial presented at EAU 2022.

Cisplatin-based chemotherapy is still the recommended first-line therapy for eligible patients with advanced urothelial cancer. However, nearly half of these patients are considered cisplatin-ineligible, with some being platinum-ineligible as well. Cisplatin-ineligible patients also have poor prognosis and often have higher comorbidity burdens.

“[As such,] clinical selection is critical to maximize the efficacy of available therapeutic options, including immunotherapy,” said Dr Roberto Iacovelli from the Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy, who presented the findings.

The ARIES study investigators sought to evaluate the efficacy and safety of avelumab in 198 patients with advanced urothelial cancer who were PD-L1 positive (n=71 had PD-L1 expression ≥5 percent) and cisplatin-ineligible. The most common reasons for cisplatin ineligibility were having a creatinine clearance of <60 mL/min (70 percent) and Eastern Cooperative Oncology Group Performance Status 2 (31 percent). The 71 PD-L1-positive participants (78 percent male) were administered IV avelumab 10 mg/kg Q2W.

As of data cut off, median follow-up was 10 months, and 14 patients were still on treatment.

Although the 1-year overall survival (OS) rate reported in the study was below the expected rate (43 percent [actuarial] vs 57 percent [expected]), a disease control rate of 44 percent was achieved with avelumab, with six patients having complete responses. Eleven patients exhibited partial response, while 14 patients had stable disease.

“First-line avelumab demonstrated activity in cisplatin-ineligible advanced urothelial cancer patients, with a notable complete response rate,” said Iacovelli.

The median OS of 10 months aligns with that observed in previous data. Median progression-free survival was 2 months.

The incidence of grade 3–5 adverse events (AEs) was low, the most common being anaemia (6 percent) followed by infusion reaction (4 percent). Other high-grade AEs reported were abdominal pain, anorexia, bone pain, fatigue, and fever (n=1 for each event). “[These findings show] the favourable safety profile of avelumab in advanced urothelial cancer,” said Iacovelli.

Avelumab has gained approval in certain countries for the management of locally advanced or metastatic urothelial cancer after disease progression during or after platinum-containing chemotherapy following the results seen in a large phase Ib study. [Lancet Oncol 2018;19:51-64; J Clin Oncol 2019;37(Suppl):425]

The current findings build on evidence reflecting the benefit of avelumab in urothelial cancer patients who have received cisplatin- and carboplatin-based chemotherapy, thus strengthening the potential of avelumab as a treatment alternative for bladder cancer. [N Engl J Med 2020;383:1218-1230]