Avelumab plus axitinib in advanced renal cell carcinoma (aRCC): 12-month interim results from a real-world observational study in the United Kingdom.
Authors: Nathan Paul D. , Muazzam Iqtedar Ahmed , Frazer Ricky , Sharma Anand , Hickey Joseph David , Ritchie Aimi Rose 
Published: February 2022

301 Background: The combination therapy avelumab + axitinib (A + Ax) has demonstrated superior progression-free survival (PFS) and objective response rate (ORR) benefit across all International Metastatic RCC Database Consortium (IMDC) risk groups (favourable, intermediate, and poor) vs sunitinib in patients with previously untreated aRCC. A + Ax is now approved and funded in the UK; on 29 October 2019, the European Commission approved A + Ax for first-line treatment of adult patients with aRCC, and it has been funded by the Cancer Drugs Fund since 30 July 2020. Here we report 12-month real-world outcomes of A + Ax in patients with aRCC in the UK. Methods: Patients ≥18 years with diagnosed aRCC who initiated A + Ax treatment outside of a clinical trial on or after 1 August 2019 via an early access to medicines scheme were recruited at 4 UK sites. Patient informed consent was obtained. Primary endpoints of interest include overall survival (OS), best response, PFS and ORR at 12 months. Descriptive statistics are provided. Recruitment is ongoing until Jan 2022 and follow-up until July 2023. Results: This analysis includes 36 patients with a minimum 12 month follow up. Median age at baseline was 66.2 (range, 39.8-84.1) years. 78% were male, 69% were White, and 6% were Asian/Asian British; ethnicities of 25% of patients were not recorded. Patient IMDC risk statuses were: 39% favourable, 42% intermediate, 17% poor, and 3% unknown; 89% had an ECOG PS of 0 or 1. Median time between aRCC diagnosis and A + Ax initiation was 1.8 months. Most patients had clear cell (72%) or other (25%) histology, had undergone nephrectomy (61%), and had 1 or 2 sites of metastatic disease (69%). The most common metastatic sites were lung (50%), bone (36%), and lymph node (25%). The 12 month OS rate was 86% (95% CI 74.8-97.4), and ORR was 53% (95% CI 36.5-69.1) with 6% achieving a complete response and 47% achieving partial response. Median duration of follow up and PFS was 12 months. Best responses within 12 months of observation were: complete response = 2 (6%), partial response = 17 (47%), stable disease = 14 (39%), and progressive disease = 3 (8%). At the time of the first and second infusions, 39% of patients received Ax at the starting dose of 5 mg twice daily, 47% had a dose escalation, and 14% had a dose reduction. Infusion-related reactions (IRRs) were recorded in 9 patients (25%) in the first 12 months, with 10 events total. All 10 IRRs required the use of high-dose corticosteroids. Median time from A + Ax initiation to IRR was 1.3 months. A + Ax was discontinued in 1 patient (3%) due to toxicity and 4 patients (11%) due to disease progression. Conclusions: In this real-world study of A + Ax treatment in the UK, A + Ax displayed comparable clinical responses to previously published data. OS, ORR, and best response figures were in line with published randomised controlled trials, which is encouraging in a nontrial population.