Impact of tumor burden on outcomes after immune versus conventional therapies.

Abstract

e20621 Background: Tumor burden has been previously suggested to be an important determinant of immunotherapy efficacy due to tumor bulk impeding lymphocyte infiltration, and a greater concentration of immunosuppressive tumor-derived factors. However, a higher tumor burden may also lead to a greater neoantigen load resulting in a greater potential for eliciting immune responses with immune checkpoint inhibitors. Whether tumor burden is a specific predictor of immunotherapy outcomes remains ambiguous. Methods: To determine whether tumor burden is associated with immunotherapy outcomes, we conducted an analysis of 2980 patients with individual-level data from eight clinical trials across four different cancer types: NSCLC, RCC, HCC, and bladder cancer. Kaplan-Meier survival analysis was used to estimate and compare survival probabilities across different treatment groups and tumor burden. Progression-free survival (PFS) and overall survival (OS) were selected as the primary survival endpoints. Patients were stratified into subgroups based on treatment modality (immune checkpoint inhibitor [ICI] therapy vs. chemotherapy) and tumor burden (low vs. high), with tumor burden defined using the sum of the longest diameters (SLD). Patients were ranked by SLD, and those in the lower half of the SLD distribution were categorized as having low tumor burden, while those in the upper half were categorized as having high tumor burden. Results: In patients with NSCLC, RCC, and bladder cancer, PFS was decreased in patients with higher tumor burden in ICI treated patients and conventional therapy treated patients. In HCC, there was no statistically significant difference in PFS between high and low tumor burden patients. Across all cancer types, OS was uniformly inferior in high tumor burden patients treated with ICI and with chemotherapy. Objective tumor response rates including partial and complete responses were decreased in patients with high tumor burden treated with either immunotherapy or conventional therapy. Conclusions: These results demonstrate that tumor burden is generally associated with worse outcomes regardless of treatment context, suggesting that tumor burden is a prognostic factor of advanced stage cancers undergoing systemic treatment rather than a predictive marker of immunotherapy. Tumor burden may thus be an important stratification factor for trials testing systemic therapies regardless of their mechanism of action.