Real-world (RW) treatment (tx) patterns and clinical outcomes in patients (pts) with metastatic renal cell carcinoma (mRCC) in the US community setting.
Authors: Cherrishe Brown-Bickerstaff, Paul R. Conkling, Rosa Banuelos, Jose Ricardo Perez-Torrealba, Tasha D. Hall, Navendu Samant, Yue Zhang
Journal: Journal of Clinical Oncology (2025)

470 Background: Multiple approved immunotherapy (IO)-based combination regimens have demonstrated efficacy as first-line (1L) tx for mRCC, but have also shown notable toxicity. These factors may lead to variations in how tx regimens are used in RW community oncology care. No direct, prospective comparison exists for FDA-approved IO-IO or IO + tyrosine kinase inhibitor (IO-TKI) combination regimens in mRCC. This study assessed 1L TKI dosing patterns and RW outcomes of pts with mRCC in a large network of US community oncology practices. Methods: A retrospective, observational, matched cohort study was conducted among pts diagnosed with mRCC in The US Oncology Network IKnowMed electronic health record database. Eligible pts were ≥21 years old at initial diagnosis; initiated 1L tx in the metastatic setting with an IO-IO (ipilimumab [ipi] + nivolumab [nivo]) or IO-TKI (nivo + cabozantinib [cabo], pembrolizumab [pem] + axitinib [axi], or pem + lenvatinib [len]) combination regimen between Jan 1, 2021 and Apr 30, 2023; and had ≥1 post-treatment visit or a record of death during the study observation period (Jan 1, 2021 – Oct 31, 2023). Across cohorts, pts were exactly matched on IMDC risk score, sex, and age (&lt;60y or ≥60y). Initial TKI dosing prescribed was summarized descriptively. Time to next treatment (TTNT) and overall survival (OS) were analyzed using the Kaplan-Meier method and univariable Cox regression. Results: A total of 308 pts, 77 in each cohort, were included with a median follow-up time of 11.0, 14.1, 8.8, and 9.2 months (mo) in the ipi + nivo, nivo + cabo, pem + axi, and pem + len cohorts, respectively. Across cohorts, 64% were male, 75% were ≥60 years of age (mean age, 65.1-66.9y), and IMDC risk score was as follows: 18% favorable, 51% intermediate, 21% poor, and 10% unknown. RW TKI dosing patterns and efficacy outcomes are described in the table.More pts initiated len (29.9%) below the recommended dose relative to cabo (15.6%) and axi (11.7%). The nivo + cabo cohort had a numerically longer median TTNT (14.3 mo) compared with the pem + axi (10 mo) and pem + len (9.4 mo) cohorts. Conclusions: TTNT analysis in a matched population suggests benefit of nivo + cabo in pts with mRCC in the RW 1L setting compared with other IO-TKI combinations. Dosing patterns suggest more pts may start len below the recommended dose relative to other TKIs. The highest 12-month OS was observed with nivo + cabo; however, additional follow-up is needed for more mature OS data. RW TKI dosing patterns and efficacy outcomes in 1L mRCC. IO-IO IO-TKI IO-TKI IO-TKI Variable Ipi + Nivo n=77 Nivo + Cabo n=77 Pem + Axi n=77 Pem + Len n=77 Initiated TKI below label recommended dose, n (%) NA 12 (15.6) 9 (11.7) 23 (29.9) Median TTNT, mo (95% CI) 8.4 (5.9-14.5) 14.3 (11.3-25.8) 10.0 (6.8-13.4) 9.4 (6.9-13.5) Hazard ratio (95% CI) 1.45 (0.96-2.18) ref 1.58 (1.04-2.38) 1.57 (1.04-2.37) 12-month OS estimate, mo 66.3 76.8 66.9 64.8