Avelumab in combination with axitinib (Ave + Axi) for first-line (1L) treatment of advanced renal cell carcinoma (aRCC): A systematic literature review (SLR) of real-world effectiveness and safety.
Authors: Mairead Kearney, Ankush Taneja, Aniket Sharma, Ahmed Elsada, Anna-Maria Fontrier, Stamatia Alexopoulos, Neil Roskell
Journal: Journal of Clinical Oncology (2025)

491 Background: Ave + Axi combination is an approved option worldwide for 1L treatment of patients with aRCC based on the results of the JAVELIN Renal 101 phase 3 trial. The results of the final analysis (data cutoff: Aug 31, 2023) confirmed the long-term efficacy and manageable safety profile of this immunotherapy (IO)/tyrosine kinase inhibitor combination with the longest follow-up (≥68 months in all patients). The aim of this SLR was to summarize the real-world effectiveness, safety, and tolerability of Ave + Axi in aRCC and compare with outcomes from JAVELIN Renal 101. Methods: A SLR was conducted using 3 online databases (MEDLINE, Embase, and Cochrane) to identify publications (to Jul 29, 2024) and recent conference abstracts of Ave + Axi real-world studies reporting outcomes for 1L treatment of aRCC, with no geographical or observational study-type restrictions. Results: A total of 9 studies met the inclusion criteria; most were retrospective (7/9), including multicenter, single-center, or database/registry studies relying on secondary data sources. Studies were conducted in the UK (4/9), Japan (3/9), USA (1/9), and Russia (1/9). Median age was 61.5-70 years; most patients were male (68%-90.5%), had an ECOG performance status of 0-1 (60%-94%), and had metastatic tumors with clear cell histology (66.7%-100%). High attrition between lines of treatment was noted, with only 35% of patients receiving second-line treatment after disease progression (most commonly with cabozantinib monotherapy, 52.2%). Median progression-free survival (PFS) ranged from 9.1-15.3 months (vs 13.9 months in JAVELIN Renal 101). Landmark 1-year PFS and overall survival rates from Ave + Axi start were 27%-68.2% and 15%-98.8%, respectively. Overall response rate was numerically higher in International Metastatic RCC Database Consortium (IMDC) risk favorable- (70.5%) vs intermediate- (64.7%) or poor-risk (39%) subgroups (reported in 1 UK study). Rates of grade ≥3 adverse events (AEs; 17%-36%) and discontinuation due to AEs (10%-27%) were low. Conclusions: Overall, findings from global real-world studies of Ave + Axi in 1L aRCC align with those of the JAVELIN Renal 101 trial, validating the long-term efficacy and safety of this combination. The high rate of attrition between lines of therapy supports the use of the most effective IO-based treatments upfront. Despite the limited number of studies and data heterogeneity, results from this SLR of real-world studies conducted in the IO era in several countries provide a good representation of Ave + Axi use in an evolving treatment landscape. Additional prospective data (eg, the ongoing multi-country AVION study; NCT04941768) and extended follow-up are required to inform the optimal use of Ave + Axi in patient subgroups, such as those with IMDC favorable-risk disease.