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. Author manuscript; available in PMC: 2021 Oct 15.

Published in final edited form as: Cell. 2020 Oct 1;183(2):363–376.e13. doi: 10.1016/j.cell.2020.09.001

Figure 2: — A) Outcomes of PD-L1 blockade treated patients from the POPLAR/OAK Cohort (Gandara et al., 2018) (POPLAR/OAK ICI Cohort) stratified by high bTMB/MB (≥14) and low bTMB/MB (<14). P-value calculated by two-sided Fisher’s Exact Test (DCB n = 139; NDB n = 290).

B) Pre-treatment ctDNA concentration (haploid genome equivalents per mL of plasma, hGE/mL) and C) ctDNA-normalized bTMB (norm. bTMB) in POPLAR/OAK ICI Cohort. P-values were calculating using a Wilcoxon test.

D) Area under the curve (AUC) for individual parameters in immunotherapy patients generated by leave-one-out cross-validation (LOOCV) ROC analysis.

E) Probability of PFS for high norm. bTMB (median = 4.14 mo.) and low norm. bTMB (median = 2.16 mo.) PD-L1 blockade patients stratified by the LOOCV-identified optimal cut-point in the POPLAR OAK ICI Cohort (n = 429).

F) Outcomes of chemotherapy treated patients from the POPLAR/OAK Cohort (Gandara et al., 2018) (POPLAR/OAK Chemo Cohort) stratified by high bTMB/MB (≥14) and low bTMB/MB (<14). P-value calculated by two-sided Fisher’s Exact Test (DCB n=118; NDB n = 306).

G) Pre-treatment ctDNA concentration and H) norm. bTMB (POPLAR/OAK Chemo Cohort) in chemotherapy patients. P-values were calculated using a Wilcoxon test.

I) Probability of PFS for high norm. bTMB (median = 3.25 mo.) and low norm. bTMB (median = 4.00 mo.) chemotherapy patients stratified by the LOOCV-identified optimal cut-point in the POPLAR/OAK Chemo Cohort (n = 424).

J) Probability of PFS for high norm. bTMB (median = 16.49 mo.) and low norm. bTMB (median = 1.92 mo.) patients who received single-agent PD-(L)1 blockade in this study, exclusive of the DIREct Validation Cohort (n = 37) stratified by the cut-point of norm. bTMB identified in the POPLAR/OAK ICI Cohort. See also Figure S2.