Barts Cancer Institute, London, United Kingdom
Thomas Powles , Chaoyu Jin , Yanan Zheng , Paul Baverel , Rajesh Narwal , Pralay Mukhopadhyay , Xiaoping Jin , Phillip A. Dennis , Ashok Kumar Gupta , Yong Ben , Tony W. Ho , Lorin Roskos
Background: Progression of cancer is often associated with biomarkers of cancer inflammation, cachexia, and increased protein catabolism. Anti-PD1 and PD-L1 therapy have demonstrated durable responses across a number of tumor types. Durvalumab is a human monoclonal antibody that binds to PD-L1 and blocks its interaction with PD-1 and CD80. The primary objective of this analysis was to prospectively assess potential correlations of longitudinal changes in ALB and NLR and durvalumab clearance (CL) rate to maximum decrease in tumor size and overall survival (OS) in patients (pts) with NSCLC and UC receiving durvalumab. Methods: Longitudinal target lesion size, serum chemistry, hematology and pharmacokinetic data were obtained from 3L+ NSCLC pts (n = 418) in study ATLANTIC and 2L+ UC pts (n = 182) in study 1108 during durvalumab treatment. Nonparametric correlations (Spearman’s rho) were evaluated between OS, maximum percent change in target lesion size, and the maximum percent change from baseline observed in ALB, NLR, and CL. Results: In NSCLC, maximum decrease in tumor size was correlated with increased ALB (r = 0.46, p < 0.0001), decreased NLR (r = 0.44, p < 0.0001), and decreased CL (r = 0.66, p < 0.0001). OS was similarly correlated with increased ALB (r = 0.47, p < 0.0001), decreased NLR (r = 0.41, p < 0.0001), and decreased CL (r = 0.76, p < 0.0001). In UC, decreased tumor size also correlated with increased ALB (r = 0.43, p < 0.0001), decreased NLR (r = 0.38, p < 0.0001), and decreased CL (r = 0.65, p < 0.0001). OS in UC also correlated with increased ALB (r = 0.50, p < 0.0001), decreased NLR (r = 0.33, p < 0.0001) and decreased CL (r = 0.82, p < 0.0001). Conclusions: In NSCLC and UC pts receiving durvalumab, tumor shrinkage and longer survival are associated with increased ALB, decreased NLR and decreased clearance of durvalumab. These findings support the hypothesis that durvalumab may be associated with a decrease in protein catabolism, inflammation and cachexia among pts who benefited from therapy. Additional biomarkers of cancer, inflammation and cachexia will be evaluated for relationships to clinical outcomes.
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