Association between tumor burden and response to immunotherapy in patients with metastatic renal cell carcinoma.

Abstract

4541 Background: Immunotherapy (IO) has become the standard of care in patients with metastatic renal cell carcinoma (mRCC), yet clinical biomarkers of outcome remain elusive. Preclinical and clinical studies have demonstrated that a lower tumor volume burden is associated with better response to IO in melanoma and lung cancer. Methods: Retrospective chart review of mRCC patients treated with Immunotherapy/Immunotherapy or Immunotherapy/Tyrosine kinase inhibitors (TKI) combinations at Vanderbilt Ingram Cancer Center was conducted. Baseline target tumor lesions including primary kidney tumors and treatment response were assessed by RECIST 1.1 criteria. The association between baseline tumor burden and outcomes of interest [progression-free survival (PFS) and overall survival (OS)] were assessed with multivariable Cox regression model. Results: 79 patients with mRCC were included in the cohort. The median age was 64, 80% were male, 82% had clear cell histology, and 73% were IMDC intermediate/poor risk group. 53% received IO/IO and 39% received IO/TKI. 71% had prior nephrectomy and 14% had prior systemic therapy. The median baseline tumor burden was 87 mm (range: 16-363 mm). After adjusting for age, gender, histology, prior nephrectomy/systemic therapy and IMDC risk, baseline tumor burden was not associated with either PFS (p-value: 0.42) or OS (p-value: 0.99). At the initial follow-up scan (median time of 3.1 months from treatment initiation) 22 (28%) patients had an objective response and 41 (52%) patients had stable disease. Among patients with tumor shrinkage, every 10% decrease seen in the sum of the target lesions was associated with improved PFS (AHR: 0.77, 95%CI: 0.63-0.94, p-value:0.009) and OS (AHR: 0.62, 95%CI: 0.42-0.93, p-value:0.02). Conclusions: While baseline tumor burden volume was not associated with clinical outcome to immunotherapy-based therapy in patients with metastatic RCC; however, the degree of early tumor shrinkage was significantly associated with better outcomes. Large tumor burden does not preclude response and good outcome to immunotherapies.