Abstract
BACKGROUND/OBJECTIVES: Cabozantinib is widely used as subsequent-line therapy after immune checkpoint inhibitor (ICI) treatment in metastatic renal cell carcinoma (mRCC), yet reliable on-treatment biomarkers are lacking. This study explored the prognostic value of a composite score combining early changes in serum albumin (ΔAlb) and the systemic immune-inflammation index (ΔSII) during cabozantinib therapy. METHODS: We retrospectively analyzed 40 patients with mRCC who received cabozantinib after prior ICI therapy. Alb and SII were measured at baseline and 6 weeks after initiation. Patients were stratified into three categories according to the ΔAlb + ΔSII composite: both favorable, either unfavorable, or both unfavorable. Progression-free survival (PFS) was analyzed using Kaplan-Meier and Cox regression models. RESULTS: Among 38 evaluable patients, PFS significantly differed across composite categories (p for trend < 0.05). Patients with both favorable changes achieved notably longer PFS, while those with both unfavorable changes experienced the shortest. Compared with the both-favorable group, the "either" and "both unfavorable" groups had shorter PFS (HR = 1.83, 95% CI 0.61-5.46; HR = 6.27, 95% CI 1.61-24.49). CONCLUSIONS: In this small retrospective cohort, early on-treatment changes in Alb and SII showed an association with PFS in ICI-pretreated mRCC treated with cabozantinib. The ΔAlb + ΔSII composite may serve as a hypothesis-generating framework, warranting confirmation in larger, prospective studies.