Metabotyping using early body weight velocity in lung cancer patients treated with pembrolizumab.

Abstract

e20527 Background: PD-L1 tumor proportion score guides immune checkpoint inhibitor therapy in advanced non-small cell lung cancer, yet outcomes remain heterogeneous. We assessed whether early on-treatment body weight velocity after pembrolizumab initiation is associated with overall survival (OS). Methods: Using the nference nSights federated platform across multiple medical centers, we retrospectively studied adults with lung cancer (ICD-10 C34.x) treated with pembrolizumab. Baseline weight was the closest measurement within 90 days pre-initiation. Percent weight change from baseline was computed at 1–6 months post-initiation (nearest weight within ±15 days). Landmark Cox models were fit independently at each timepoint for OS, adjusting for age, sex, baseline weight, baseline BMI when available, and time from diagnosis to treatment initiation. Model discrimination was assessed with the concordance index. Results: A total of 5,748 patients met inclusion criteria. Baseline demographic and clinical characteristics, including age at treatment initiation, body weight, body mass index, and time from diagnosis to treatment, were captured for all patients. Across all evaluated timepoints, percent weight gain following pembrolizumab initiation was significantly associated with improved overall survival after adjustment (hazard ratio per 1% weight change range: 0.954–0.961; all p < 0.0001). Effect estimates were similar across 1–6 month landmarks. Model discrimination increased modestly with longer follow-up (C-index 0.582 at 1 month; 0.613 at 6 months). At the 6-month landmark, 2,158 deaths were observed among 3,970 patients and each 1% weight gain was associated with lower mortality risk (HR 0.961; 95% CI 0.956–0.966). A 5% increase in body weight corresponded to an estimated 18–21% lower mortality hazard, whereas a 5% decrease corresponded to an estimated 22–27% higher mortality hazard, holding covariates constant. Conclusions: Early on-treatment body weight velocity is a low-burden routinely collected measure consistently associated with OS during pembrolizumab therapy. Weight-velocity metabotyping may complement tumor and host biomarkers for pragmatic risk stratification and supportive-care assessment, supporting scalable value-conscious care. Association between weight change and overall survival in lung cancer patients treated with pembrolizumab. HR <1 indicates weight gain is associated with reduced mortality risk. Timepoint Patients Events C-index Weight Change HR 95% CI p-value 1 month 5548 3172 0.582 0.958 0.949-0.966 <0.0001 2 months 5339 3094 0.601 0.954 0.947-0.96 <0.0001 3 months 5034 2868 0.608 0.958 0.952-0.963 <0.0001 4 months 4624 2609 0.61 0.957 0.952-0.963 <0.0001 5 months 4199 2370 0.612 0.959 0.954-0.965 <0.0001 6 months 3970 2158 0.613 0.961 0.956-0.966 <0.0001