Validation of a 15-gene prognostic signature in metastatic clear cell renal cell carcinoma.

• DOI: 10.1200/jco.2025.43.5_suppl.578
• Publication Date: 2025-02-18T14:33:57Z
• Authors: Steven Monda; Srinivas Nallandh...; Ulka N. Vaishampayan; Udit Singhal; Zayne Knuth; Rohit Mehra; Samuel Kaffenberger; Khaled Hafez; Aaron M. Udager; Ganesh S. Palapattu; Todd Matthew Morgan; Simpa Samuel Salami
• Keywords: Gene signature

578 Background: Our group previously developed and validated a 15-gene prognostic signature (15G score) in localized clear cell renal carcinoma (ccRCC). Giving its ability to differentiate aggressive indolent disease the setting, we sought apply 15G score patients with metastatic ccRCC evaluate score’s performance across different treatments. Methods: We analyzed 2,121 from four major trial datasets: IMmotion 150 (IMM150), Immotion 151 (IMM151), Javelin Renal 101 (JR101), Checkmate 009, 010, 025 (CM009/010/025). Treatment control arms all trials were included grouped within treatment groups which atezolizumab, atezolizumab plus bevacizumab, sunitinib, avelumab axitinib, nivolumab, everolimus. The score, originally derived established be ccRCC, was calculated using z-score transformed RNA-seq data each arm of classify into high-risk versus low-risk threshold. tested association progression free survival (PFS) Cox proportional hazards analyses without controlling for MSKCC risk. Results: On univariable analysis, associated significantly worse PFS five seven (Table). Worse observed everolimus (HR [95% CI]: 2.8 [1.6-4.9],1.7 [1.4-2.2], 1.7 [1.4-2.0], 1.5 [1.1-2.2]. Within IMM151 CM009/010/025, where risk available, independently while [1.2-2.0], 1.6 [2.3], p<0.05). overall (OS) OS [1.0-2.2]) but did not reach significance nivolumab 1.4 [0.9-2.0]). Conclusions: among diverse cohort receiving systemic therapy regimens. compared analysis group. Group Trials scoreLow-risk (n) scoreHigh-risk p-value HR (95% CI) Immunotherapy Atezolizumab IMM150 45 41 <0.001 2.8(1.6, 4.9) Nivolumab CM009/010/025 74 106 0.06 1.4(1.0, 1.9) Combination Atezolizumab+Bevacizumab IMM151/150 218 277 1.7(1.4, 2.2) Avelumab+Axitinib JR101 152 202 0.09 1.3(1.0, 1.8) TKI / MTORi Sunitinib IMM150/IMM151/JR101 370 507 2.0) Everolimus 51 78 0.03 1.5(1.1,