Abstract 1073P
Background
Basal hypermetabolism (increased resting energy expenditure (REE) by more than 10%) was recently correlated with worse response to anti-PD1 immunotherapy in metastatic non-small cell lung cancer patients (NSCLC) in the ELY study. Hypermetabolic patients are at risk of malnutrition and cachexia which are known to be deleterious prognostic factors and to affect nivolumab elimination clearance (CL). We aimed to evaluate the association between basal metabolism and nivolumab CL, and whether these both variables are predictive factors of nivolumab efficacy in NSCLC patients included in the ELY study (NCT04879316).
Methods
REE was measured (mREE) using ambulatory indirect calorimetry and compared with the theoretical value (tREE) prior to treatment initiation. Nivolumab trough plasma concentrations (Cmin) were measured, then analyzed using population approach in Monolix. The primary endpoint was progression-free survival (PFS). Survival analysis was performed using Cox proportional hazard models.
Results
98 patients (median age 67 y [min-max 41-84], 68% male) were included in the analysis and contributed 324 nivolumab Cmin. Basal metabolism was available for 91 patients. Baseline albumin was inversely correlated with nivolumab CL (p=0.0003). Total body weight (TBW) was correlated with central volume of distribution (p=0.002). Median PFS was 3.5 months (CI95=2.7-4.8). In the univariate Cox analysis, nivolumab CL (p=0.012), baseline CRP (p=0.02), basal metabolism (p=0.00001) and TBW loss >5% in the last 3 months (p=0.07) were significantly associated with PFS. In the multivariate step, nivolumab CL ≥ median (HR=1.71, CI95=1.05-2.77, p=0.03), basal metabolism (HR=3.39, CI95=1.90-6.04 for hyper- vs hypo- or normometabolism, p=0.00003) and TBW loss >5% (HR=2.66, CI95=1.53-4.62, p=0.0005) were independently associated with shorter PFS.
Conclusions
Basal hypermetabolism did not influence nivolumab CL but both variables were independent predictors of PFS in NSCLC patients. These results suggest that basal hypermetabolism not only reflects cachexia but also a reduced ability of the patient to develop an active immune response to nivolumab.
Clinical trial identification
NCT04879316.
Editorial acknowledgement
Legal entity responsible for the study
Prof François Goldwasser.
Funding
Baxter (Grant Number 04012016).
Disclosure
All authors have declared no conflicts of interest.