Serum test identifies patients deriving benefit from CPIs 185 5 pooled second-line population, multivariate analysis showed that the resistant vs not resistant stratification was a significant independent predictor of OS (P<0.001) and PFS (P=0.006) when adjusted for multiple baseline factors, Table 2. The sensitive vs not sensitive stratification was a significant independent predictor of OS (P=0.009) and showed a trend to prediction of PFS (P=0.079). Figures 3E and 3F show OS for classification groups obtained by applying the test to pretreatment samples of the chemotherapy cohort, in which patients received docetaxel as second-line therapy. There was no indication that the test was able to stratify patients by outcome following this single agent chemotherapy (P=0.471 and P=0.165 for OS comparison of resistant vs not resistant and sensitive vs not sensitive, respectively). Protein set enrichment To examine the potential biological mechanisms underlying the test, the association of test classification with various biological processes was assessed using PSEA methods22-24. The results are summarized in Table 3. Acute phase response, acute inflammatory response, wound healing, and complement activation were identified as associated with test classification with P<0.001. Additionally, innate immune response and chronic inflammatory response were identified as associated with P<0.01. Similar analysis was performed comparing the sensitive subgroup with the remaining patients. Only immune tolerance and suppression were identified as associated with test classification with P<0.01 (FDR<0.1). Full results for sensitive vs not sensitive phenotype are contained in the Supplemental Data: Results Supplementary Table 21.
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