Combination treatment with anti-angiogenic agents and immune checkpoint inhibitors has demonstrated significant efficacy in advanced renal cell carcinoma (RCC). However, data on treatment-emergent renal injury during combination therapy and its prognostic implications remain limited. This study analyzed renal injury and its association with survival outcomes in patients with advanced RCC receiving first-line benmelstobart combined with anlotinib in the ETER100 trial.
All randomized patients in the ETER100 (NCT04523272) trial treated with at least one dose of study treatment were included in this analysis. Baseline characteristics, laboratory test results, and information on objective responses, disease progression, and death events were collected. The primary outcomes of this study included renal function changes during therapy, risk factors for renal function abnormalities, clinical outcomes of patients with renal function abnormalities, and the association between renal function abnormalities and survival outcomes.
Compared with sunitinib monotherapy, patients receiving benmelstobart combined with anlotinib showed no significant differences in the incidence of serum creatinine elevation (p = 0.0538), percentage decrease in creatinine clearance (p = 0.2546), absolute decrease in creatinine clearance (p = 0.7343), or proteinuria (p = 0.0728). Multivariate analysis identified a history of nephrectomy and estimated glomerular filtration rate <90 mL/min/1.73 m² as independent predictors of serum creatinine elevation in patients receiving combination therapy. As of January 2024, 64.00% of patients (64/100) who developed serum creatinine elevation during combination therapy had recovered to normal levels, and 6.00% (6/100) showed improvement. Besides, 45.56% of patients (77/169) who had proteinuria recovered to normal, and 22.49% (38/169) experienced improvement. Multivariate Cox regression analysis showed that both serum creatinine elevation (progression-free survival [PFS]: p = 0.3526; overall survival [OS]: p = 0.0521) and proteinuria (PFS: p = 0.5831; OS: p = 0.1224) were not independent risk factors for progression-free survival or overall survival in patients receiving combination therapy.
For patients with advanced RCC in the ETER100 trial, combination therapy with anti-angiogenic agents and immune checkpoint inhibitors did not increase the risk of renal injury, and in this treatment context, renal function abnormalities occurring during treatment were not significantly associated with survival outcomes.
ClinicalTrials.gov identifier: NCT04523272.
BMC medicine. 2026 Jul 01 [Epub ahead of print]
Juan Li, Huichun Tian, Huayan Xu, Xieqiao Yan, Bixia Tang, Siming Li, Li Zhou, Xiaowen Wu, Zhihong Chi, Chuanliang Cui, Lu Si, Jun Guo, Xinan Sheng
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China., Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, 100142, China., Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China. .