The Effect of Weight Change During Treatment With Targeted Therapy in Patients With Metastatic Renal Cell Carcinoma

Background: The relationship between weight change during treatment and survival remains poorly characterized in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods: In this retrospective analysis we included 3311 patients with mRCC treated in phase II/III first-line or second-line targeted therapy clinical trials and assessed the effect of weight change on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) at 6 and 12 weeks from treatment initiation. Weight change was defined as weight loss (≥5% reduction), weight gain (≥2% increase), or stable weight from baseline. Survival analyses were performed using the Kaplan–Meier method and adjusted for known prognostic factors using Cox regression multivariable analysis. Results: Overall, 1916 (58%) had stable weight, 936 (28%) had weight loss, and 459 (14%) had weight gain at 12 weeks. Patients with weight loss at 12 weeks had inferior OS compared with those with stable weight (hazard ratio [HR], 1.494; 95% confidence interval [CI], 1.322-1.688; P < .0001; median OS 18.7 vs. 26.9 months), and shorter PFS (HR, 1.315; 95% CI, 1.189-1.455; P < .0001; median PFS, 7.2 vs. 10.1 months). The ORRs for patients with weight loss, stable weight, and weight gain at 12 weeks were 23.4% (n = 219/936), 32.1% (n = 615/1916), and 35.9% (n = 165/459), respectively (adjusted odds ratio, 0.715; P = .03). Findings were consistent at 6 weeks. Adverse events were similar between groups. Conclusion: We showed that mRCC patients who experience weight loss during treatment have worse outcomes compared with patients with stable weight at 6 and 12 weeks of treatment. Weight loss at 6 weeks from treatment initiation might be an early clinical biomarker of worse survival and might provide prognostic utility.