976P - Efficacy of immune checkpoint inhibitors (ICI) and genomic alterations by body mass index (BMI) in advanced renal cell carcinoma (RCC)

Abstract

BackgroundAn elevated BMI is associated with improved prognosis in certain solid tumors treated with ICI; however, real-world data and genomic analysis has been lacking. We investigated the effect of BMI on RCC patients treated with PD-1/PD-L1 based ICI and explored potential genomic alterations (GA). MethodsUsing the International Metastatic RCC Database Consortium (IMDC) database, we performed a retrospective analysis on patients treated with ICI alone or in combination with other therapies. The association of BMI with overall survival (OS), time to treatment failure (TTF), and objective response rate (ORR) was evaluated using Cox and logistic regressions respectively, adjusted for IMDC risk groups, histology, line and type of therapy, age, gender, and race. In an exploratory analysis of patients with clear cell RCC and available NGS panel data (275-447 genes), GA frequencies and tumor mutational burden (TMB) were compared by BMI status using Fisher’s exact and Mann-Whitney U tests. Results were considered statistically significant if p<0.05 or q<0.10. ResultsOf 1055 eligible patients, 735 had BMI data at start of ICI. Median follow up was 13.5 (<1-78.6) months (mos). Patients were mostly male (76%), had clear cell histology (85%), and were intermediate risk (60%). Overall, 31% received first-line ICI and 31% received combination ICI (19% with VEGF, 12% with CTLA-4/other therapies). At ICI initiation, 274 (37%) patients were considered low BMI (<25kg/m2) and 461 (63%) considered high BMI (≥25kg/m2). Patients with high BMI had better OS compared to those with low BMI, with 1-yr OS 79% vs 66% (adjusted HR=0.75, 0.57-0.97, p=0.03). ORR (30% vs 21%, adjusted p=0.06) and TTF (median 7.4 vs 4.9 mos, adjusted p=0.8) did not statistically differ. In a subset of 319 patients with clear cell RCC and available NGS data, GA and TMB (6.81 vs 6.81 mut/Mb, p=0.9) were found to be similar between those with high BMI compared to low BMI. ConclusionsHigh BMI is associated with improved OS in advanced RCC patients treated with ICI. In an exploratory analysis, there were no differences in genomic alterations on NGS by BMI status. Further correlative work is ongoing. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureS.K. Pal: Advisory / Consultancy: Astellas; Advisory / Consultancy: Aveo; Advisory / Consultancy: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Myriad; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): Medivation. A.R. Hansen: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Pfizer. F. Donskov: Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer. T. Yuasa: Advisory / Consultancy: BMS; Advisory / Consultancy: Novartis; Advisory / Consultancy: Ono; Advisory / Consultancy: Pfizer. U. Vaishampayan: Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy: Genentech; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Sanofi. N.S. Basappa: Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Janssen; Advisory / Consultancy: Merck; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche. D.Y.C. Heng: Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Janssen. T.K. Choueiri: Advisory / Consultancy: Alexion; Advisory / Consultancy: Alligent; Advisory / Consultancy: Analysis Group; Research grant / Funding (institution): Agensys; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Cerulean; Advisory / Consultancy, Research grant / Funding (institution): Corvus; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Foundation Medicine; Advisory / Consultancy, Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (institution): Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Peloton; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Prometheus; Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech. All other authors have declared no conflicts of interest.