Association of dietary fiber and fructose with progression-free survival (PFS) in metastatic/advanced urothelial cancer (mUC) on immune checkpoint blockade (ICB) independent of correlates of metabolic health.

Abstract

e16569 Background: Diet can modulate the gut microbiome and may affect ICB efficacy. In a cohort of pts with mUC on ICB, we previously reported associations of longer PFS with high dietary fiber and low dietary fructose. These associations were independent of clinical factors. However, observational studies can be affected by confounding, so we sought to determine if confounding by predictors of metabolic health explained our prior findings. Methods: In a retrospective analysis of a prospectively collected cohort, we leveraged dietary data collected with the Harvard Willett Food Frequency Questionnaire from pts with mUC initiating ICB at Memorial Sloan Kettering to assess for associations between PFS and baseline BMI, daily caloric intake (cal/d), and dietary glucose. These were treated as continuous variables and log transformed if skewed. Associations with PFS were assessed by univariate (UV) & multivariable (MV) Cox proportional hazards regression. Results: From 2/2021-6/2022, 38 pts eligible for analysis enrolled. Median follow-up was 10.4 months with 27 PFS events. Median (with interquartile range) for each variable of interest: fiber 17 g/day (13-22); fructose 15 g/day (12-31); BMI 26.5 kg/m2 (23.4-30.4); glucose 15 g/day (11-25); cal/d 1,597 (1,091-1,939). Visceral metastases were present in 21 (55%) pts, and 5 (13%) had prior ICB. BMI, glucose, and cal/d were not associated with PFS in UV models (BMI HR 0.27, 95% CI 0.02-3.29, p=0.31; glucose HR 1.46, 95% CI 0.74-2.86, p=0.27; cal/d HR 0.74, 95% CI 0.30-1.79, p=0.50), models adjusted for tumor mutational burden, Bellmunt risk factors, and prior ICB (BMI HR 0.34, 95% CI 0.02-4.96; p=0.43; glucose HR 1.3, 95% CI 0.63-2.64, p=0.49; cal/d HR 0.51, 95% CI 0.19-1.40, p=0.19), nor models adjusted for fiber and fructose intake (BMI HR 0.27, 95% CI 0.02-3.11; p=0.29; glucose HR 0.51, 95% CI 0.06-4.61, p=0.55; cal/d HR 0.67, 95% CI 0.13-3.45, p=0.63). Associations of fiber and fructose intake with PFS persisted after adjusting for BMI, glucose, and cal/d (Table 1). Conclusions: In mUC, BMI, cal/d, and dietary glucose were not associated with PFS on ICB. Confounding by these variables did not account for associations of high dietary fiber and low dietary fructose with longer PFS. Hazard ratios (HR) with 95% confidence intervals (CI) for PFS. All MV models included fiber & fructose. Dietary variable UV models Model for fiber & fructose together Adjusted for BMI Adjusted for glucose intake Adjusted for cal/d Fiber, g/day 0.98 (0.94-1.02); p = 0.28 0.90 (0.84-0.97); p = 0.005 0.91 (0.85-0.97); p = 0.004 0.91 (0.84-0.97); p = 0.008 0.91 (0.84-0.996); p = 0.04 Fructose, log(g/day) 1.66 (0.89-3.09); p = 0.11 5.02 (2.06-12.23); p = 0.0004 5.06 (2.08-12.32); p = 0.0004 8.65 (1.16-64.30); p = 0.035 5.44 (2.08-14.18); p = 0.0005