Baseline radiological tumor burden to sub-stratify IMDC risk groups in metastatic renal cell carcinoma treated with first-line therapy: A post hoc analysis from a randomized phase III trial.

4544 Background: Baseline radiological tumor burden (BRTB) is a measurement derived from routine CT scans and reflects baseline tumor burden. Herein we assess the utility of BRTB to help with risk assessment within IMDC risk subgroups from a randomized prospective phase III study. Methods: We reviewed data of 701 patients with metastatic renal cell carcinoma (mRCC) from the CheckMate 9ER trial (Choueiri, NEJM 2021). Patients with BRTB measurement per investigator using RECIST v1.1 at baseline were included. Outcomes of interest included overall survival (OS), and progression-free survival (PFS). To evaluate the impact of BRTB on OS and PFS, we used univariate and multivariable Cox regression models for each IMDC subgroup accounting for age, sex, race, stage at diagnosis, sarcomatoid features and regimen type (IO+VEGFi, VEGFi). Results: Favorable, intermediate and poor risk IMDC subgroups included 157/701, 392/701 and 132/701 patients, respectively. This cohort included 63, 187 and 94 OS events and 112, 290 and 103 PFS events in favorable, intermediate and poor risk groups, respectively. For the favorable risk group, BRTB was not associated with OS or PFS on multivariable analysis (HR adjusted = 1.00, 95%CI: 0.99-1.01, p = 0.68 and HR adjusted = 1.00, 95%CI: 0.99 – 1.00, p = 0.99, respectively). Similarly for the poor risk group, BRTB was not associated with OS or PFS on multivariable analysis (HR adjusted = 1.03, 95%CI: 0.99-1.06, p = 0.06 and HR adjusted = 1.02, 95%CI: 0.98 – 1.04, p = 0.54, respectively). However, in the intermediate risk group, higher BRTB was associated with worse OS (HR: 1.05 for each 1 cm increase in BRTB, 95%CI: 1.04-1.07, p < 0.0001) and PFS (HR: 1.03, 95%CI: 1.01-1.05, p < 0.001). On multivariable analysis, BRTB remained associated with both OS and PFS (HR adjusted = 1.05, 95%CI: 1.04-1.07, p < 0.0001 and HR adjusted = 1.03, 95%CI: 1.02 – 1.05, p < 0.0001, respectively). Further, we stratified IMDC intermediate risk group outcomes according to BRTB median value of 6.33cm (Table). Conclusions: While BRTB does not appear to predict outcomes in favorable and poor-risk subgroups in this study, BRTB is a useful metric for sub-stratification of the intermediate-risk IMDC subgroup. External validation is imperative to validate these findings and explore BRTB integration into clinical decision-making in mRCC. Stratification of the intermediate IMDC risk group according to baseline radiological tumor burden median (6.33cm). Intermediate low BRTB (n=196) Intermediate high BRTB (n=196) Log rank p value Median OS, months(95% CI) NR (49.5 – NR) 30.9 (24.4 – 40) p < 0.0001 Median PFS, months(95% CI) 15.84 (11.83 – 18.3) 8.41 (6.97 – 11.1) p < 0.001