Real-world treatment pattern and clinical outcomes among patients with metastatic renal cell (mRCC) carcinoma post PD-1/PD-L1 immuno-oncology (IO) therapies.
Authors: Neil J. Shah, Rahul Ravilla, Andrew J. Osterland, Karen Todoroff, Ching-Yu Wang, Pratik Rane, Hakim Saal, Ding Wang, Robert J. Motzer
Journal: Journal of Clinical Oncology (2025)

501 Background: Since its approval, PD-1/PD-L1 IO therapies are used greatly among patients with mRCC. However, outcomes in the post-IO setting are not well characterized. This study aims to characterize the treatment patterns and clinical outcomes of patients with mRCC who have experienced progression following IO therapy. Methods: A retrospective review of electronic health records from a US community oncology network included patients with mRCC who progressed on their initial IO therapy and received subsequent therapies between 01/01/2018 and 01/31/2023. The index regimen was defined as the therapy administered after the initial IO therapy, and the index date marked the initiation of this index regimen. The index line of therapy (LOT) was defined as the treatment setting in which index regimen was used. Descriptive statistics were used to summarize patient characteristics and treatment patterns. Real-world progression free survival (rwPFS) and overall survival (OS) were analyzed by Kaplan–Meier method. Log-rank tests were performed to compare outcomes across various Index LOTs and index regimen classes. Results: The study identified 299 patients with a median age of 68 years (IQR 60-75). Among them, 72.7% were male, 84.7% were white, and 87.4% had an intermediate/poor risk score according to the international metastatic RCC database consortium. The index regimen was given as follows: 1.7% in first line (1L), 67.9% in 2L, and 30.4% in 3L. Tyrosine kinase inhibitor (TKI) monotherapy was the most common index regimen class (62.2%) with cabozantinib being the most used regimen (46.5%). Over a median follow up of 11.3 months, median (95% CI) rwPFS and OS were 6.0 (5.4, 6.8) and 14.3 (12.1, 16.4) months, respectively. No differences were observed in rwPFS and OS across index LOTs (rwPFS p= 0.763; OS p= 0.885) or index regimen classes (rwPFS p= 0.721; OS p= 0.747, Table 1.). Conclusions: Treatment outcomes in the post-IO setting for mRCC patients are limited. TKI monotherapies are the most common treatments in this setting. No difference was found in OS or rwPFS across index LOTs and index regimen classes. Novel treatments are needed to improve clinical outcomes in these setting. Subgroups N Median rwPFS (95% CI) Median OS (95% CI) Overall 299 6.0 (5.4, 6.8) 14.3 (12.1, 16.4) Index Regimen 2L* 203 6.0 (5.0, 7.1) 14.1 (11.5, 16.3) Index Regimen 3L 91 6.0 (5.1, 8.2) 14.5 (11.6, 20.1) Index Regimen Class: IO + IO** 25 3.6 (2.8, 6.7) 19.7 (12.4, 33.3) Index Regimen Class: IO + TKI 52 5.4 (3.6, 8.0) 13.4 (9.6, 23.8) Index Regimen Class: TKI Only 186 6.7 (5.6, 8.5) 14.4 (11.6, 16.7) Index Regimen Class: Other 28 5.4 (2.9, 8.0) 13.9 (6.9, 26.9) *Due to small sample sizes of the index regimen 1L, log-rank test was performed between index regimen 2L and 3L subgroups. **Due to small sample sizes of IO only subgroup, log-rank test was performed among IO + IO, IO + TKI, TKI only, and other subgroups.