3234 - Associations between Obesity and Survival in Metastatic Renal Cell Cancer Patients Receiving Immunotherapy

12:45pm - 02:00pm PT

Hall F

Screen: 5

POSTER

Presenter(s)

Daniel Yang, MD - University of Texas Southwestern Medical Center, Dalals, TX

H. Ghaderi¹, J. J. Shi², Q. Qin³, C. Jiang³, T. Zhang⁴, R. Hannan⁵, and D. X. Yang⁵; ¹Medical Artificial Intelligence and Automation Laboratory, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, ²School of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, ³Division of Hematology and Oncology, Department of Internal Medicine, University of Texas Southwestern, Dallas, TX, ⁴Department of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX, ⁵Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX

Purpose/Objective(s): Patients with metastatic renal cell carcinoma (mRCC) comprise a heterogeneous group with varying responses to immune-checkpoint inhibitors (IO) and other systemic therapies. Some studies suggest that increased obesity may be linked to more favourable cancer outcomes among patients with mRCC, especially those receiving IO, a phenomenon often referred to as an "obesity paradox.” However, obesity associations with real-world treatment selection and subsequent IO efficacy remain unclear.

Materials/Methods: We performed retrospective cohort analysis using the nationwide Flatiron Health electronic health record-derived de-identified database, including patients diagnosed with mRCC between January 1, 2011, and October 30, 2023. Patients were categorized into five body mass index (BMI) groups: underweight (<18.5), normal (18.5-24.9), high (25-29.9), obesity (30-49.9), and extreme obesity (>50). Survival analyses were conducted using Kaplan-Meier method and statistical significance assessed via log-rank tests. Cox proportional hazards models were used to describe associations between BMI and progression-free survival (PFS) and overall survival (OS). Inverse probability weighting based on propensity scores was applied to balance BMI groups based on key variables, including type of therapy, race, age at diagnosis, ECOG performance status, stage at diagnosis, histology, and nephrectomy, smoking status, gender, payer category, and socioeconomic status (SES) index.

Results: 3,974 patients who received either pembrolizumab, ipilimumab, and/or nivolumab as part of their first-line systemic treatment were included for analysis. Increased BMI had a statistically significant association with improved PFS (log-rank p < 0.001) and OS (log-rank p < 0.001), with a median PFS of 9.6 months for obese patients and 7.5 months for normal weight patients. In multivariable Cox model analysis, patients with extreme obesity (HR = 0.86, p = 0.38), obesity (HR = 0.87, p = 0.04), and high BMI (HR = 0.88, p = 0.03) had a longer PFS compared to those with normal BMI, while underweight patients had a higher risk of progression (HR = 1.68, p = 0.03). Similarly, extreme obesity (HR = 0.71, p = 0.79), obesity (HR = 0.75, p < 0.001), and high BMI (HR = 0.85, p = 0.03) were associated with improved OS, whereas underweight patients were observed to have higher risk of mortality (HR = 1.59, p = 0.05).

Conclusion: Higher BMI was associated with improved PFS and OS for patients with mRCC receiving IO among a large real-world cohort. These findings contribute to the growing body of evidence suggesting an association between patient body composition and IO outcomes. Future research is needed to better understand the biological underpinnings of these findings and their potential impact on treatment selection.