Extended Data Fig. 1: Clinical and gut microbiome characteristics of the CA209-538 clinical trial cohort.
From: A gut microbial signature for combination immune checkpoint blockade across cancer types
a, Kaplan-Meier curve of progression-free survival stratified by histology (UGB n = 38, NEN n = 32, GYN n = 36). Log-rank test p-value for OS duration across groups printed. Chi-squared test p-value shown for proportion of OS12 per group printed. b, Kaplan-Meier curve of progression-free survival stratified by histology (UGB n = 38, NEN n = 32, GYN n = 36). Log-rank test p-value for PFS duration across groups printed. Chi-squared test of independence p-value shown for proportion of PFS12 per group printed. c, Boxplots of patient baseline blood albumin (g/L) and NLR levels (log-transformed) by BOR category (cPD n = 21, PD n = 30, SD n = 29, PR n = 22, CR n = 4). Boxplot centre line= median; box limits= upper and lower quartiles; whiskers= 1.5x interquartile range. Linear model line-of-best-fit for respective variables (albumin and NLR) versus BOR (with shaded 95% confidence interval) superimposed (in grey). Kendall τ and p-value for association between respective variables (albumin and NLR) and BOR printed. Pairwise Mann-Whitney U test p-values for cPD vs other groups summarized (*: p < 0.05, **: p < 0.01, ***: p < 0.001). Exact p-values as follows: Albumin: cPD vs PD p = 0.0076, cPD vs SD p = 0.00079, cPD vs PR p = 0.0039, cPD vs CR p = 0.034; NLR: cPD vs PD p = 0.00093, cPD vs SD p = 0.00042, cPD vs PR p = 0.0075, cPD vs CR p = 0.025. d, Proportion of explained variance (R2) of microbial composition by each available clinical and technical metadata variable. Calculated using PERMANOVA on inter-sample Aitchison distance (9999 permutations). Metadata variables coloured by category (blood, exposome, patient, technical or tumour). PERMANOVA p-values summarized (*: p < 0.05). Exact p-values available in Supplementary Table 6 (‘ca209-538_permanova’). e, Analysis of baseline microbial variance by moving PFS cut-off (1-monthly intervals, from 1-24 months). Top panel show microbial variance between groups formed by cut-off (inverse PERMANOVA p-value, 999 permutations) using Aitchison distance. Bottom panel shows proportion of progression-free-survivors at respective threshold (that is the proportion in each group). Dashed line with * indicates p = 0.05 threshold. Exact p-values available in Supplementary Tables 7 (‘moving_pfs_permanova’). Acronyms: UGB = upper gastrointestinal & biliary, NEN = neuro-endocrine neoplasms, GYN = gynaecological, PFS = progression-free survival, OS = overall survival, BOR = best overall response, CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease, cPD = clinical progressive disease, chemo = chemotherapy, PPI = proton-pump inhibitor, BMI = body-mass index, LDH = lactate dehydrogenase, NLR = neutrophil:lymphocyte ratio, ECOG = eastern cooperative oncology group, PERMANOVA = permutational multivariate analysis of variance.
