Real-world community oncology-based treatment patterns for first line axitinib plus pembrolizumab in advanced renal cell carcinoma: Initial dosing, dose reductions and clinical outcomes.
Authors: Kevin Kayvan Zarrabi, Yaa Ababio, Anthony Eccleston, Dharanija Rao, Scott Kelly, Jane Chang, Kelechi L. Adejumo, Sarah Lucht, Caleb Paydar, Bryce A Van Doren, Emily Bland, William S John, Bruce A. Feinberg, Neil J. Shah
Journal: Journal of Clinical Oncology (2025)

487 Background: Axitinib (AXI) with pembrolizumab (PEM) is approved for first line (1L) treatment of advanced renal cell carcinoma (aRCC). This study provides real-world evidence of treatment patterns and outcomes in 1L aRCC patients treated in primarily community practice settings. Methods: This retrospective, multicenter, community oncologist-based chart review study used the Cardinal Health Oncology Provider Extended Network (OPEN). Patients with age ≥18 years, stage IV clear cell aRCC diagnosis, 1L AXI+PEM initiation between 22-Apr-2019 to 22-Feb-2024, and ≥6 months follow-up were included. Descriptive statistics were used to report demographics and treatment patterns. Duration of therapy (rwDOT) was defined as start date to discontinuation date of 1L AXI+PEM (any cause). Progression-free survival (rwPFS) was defined as start of 1L AXI+PEM to physician-reported progression or death. Results: Physicians (n=25) abstracted data for 300 patients, who were a median age of 66.7 years (interquartile range [IQR]: 60.0-72.8), 61.0% (n=183) male, 69.3% (n=208) White, and 11.3% (n=34) with sarcomatoid features. International Metastasis RCC Database Consortium risk groups for patients were 18.0% favorable, 59.3% intermediate, and 21.7% poor risk (n=3 unknown). Median follow-up overall was 12.3 (IQR: 8.1-21.6) months. Most patients (95%; n=285) started AXI at the initial recommended dose of 5 mg twice daily (BID; Table). Few patients (14.3%; n=43) required AXI dose reductions, with a median time to first AXI dose reduction of 2.3 months (IQR: 1.4-3.7), while 8.7% (n=26) of patients were able to dose escalate (7.3% [n=22] to 7 mg BID; 1.3% [n=4] to 10 mg BID). At data collection, 44.7% (n=134) of patients had discontinued AXI+PEM (78.7% due to progression; 7.8% due to adverse events). Median rwDOT of 1L AXI+PEM was 11.7 (IQR: 7.0-18.5) months and 12-month rwPFS was 74.3% (95% confidence interval: 68.3-79.4). Conclusions: This is one of the first comprehensive studies to describe real-world treatment patterns and clinical outcomes of 1L AXI+PEM for aRCC patients in the US community setting. The majority of patients were able to start 1L AXI+PEM at the FDA-recommended initial dose, with a minority of patients requiring dose reductions. Further prospective studies investigating the impact of 1L AXI+PEM treatment modification on clinical outcomes for aRCC are needed. Initial AXI regimen: 5 mg orally BID (n, %) 285, 95.0 Time from 1L initiation to first AXI decrease (months; median, IQR) 2.3, 1.4-3.7 Time from 1L initiation to first AXI increase (months; median, IQR) 0.5, 0.5-2.8 AXI dose/frequency after first decrease (n, %) 43, 14.3 3 mg orally BID 36, 83.7 2 mg orally BID 6, 14.0 Other ( 2 mg BID, 2 weeks on 1 week off) 1, 2.3 AXI dose/frequency after first increase (n, %) 26, 8.7 7 mg orally BID 22, 84.6 10 mg orally BID 4, 15.4