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. 2020 May 7;3(6):e201900545. doi: 10.26508/lsa.201900545

Figure 7. MAPK pathway mutations may predict patient outcomes with immune checkpoint inhibitors independent of tumor mutational burden (TMB).

Figure 7.

(A) MAPK pathway mutations (10 genes) are associated with good clinical outcome from an independent cohort of Samstein et al (2019) in advanced or metastatic pan-cancer patients (N = 1,662) treated with PD1/PD-L1 or CTLA4 inhibitors. (B) A pie chart showing 34% patients with somatic MAPK pathway mutations in both TMB-high and TMB-low groups of patients in the pan-cancer dataset. High-TMB was previously defined as top 20% cutoff (i.e., TMB value ≥10.3 for head and neck squamous cell carcinoma [HNSCC]), whereas low-TMB represented the remaining 80% of patients (i.e., TMB value < 10.3 for HNSCC) per original publication by Samstein et al (2019). (C) Overall survival (OS) curves of four subgroups of patients: TMB-high with MAPK mutations, TMB-high with MAPK-WT, TMB-low with MAPK mutations, and TMB-low with MAPK-WT in the Samstein study. (D) Kaplan–Meier OS curves for MAPK pathway-mutated HNSCC patients versus MAPK pathway WT patients (MSS ICI pan-cancer cohort; N = 249). (E) Kaplan–Meier OS curves for MAPK pathway-mutated HNSCC patients versus MAPK pathway WT patients (study by Samstein et al (2019); HNSCC Ooal subsite cohort; N = 47). (F) Table of Fisher’s exact test showing association of HNSCC subtypes with the immune class as defined by Chen et al (2019). (G) In HNSCC patients with distant metastases (lung, liver, heart, brain, and bone), MAPK pathway mutations are associated with better OS upon PD1/PD-L1 inhibitor treatment (P = 0.0489; based on databases from Samstein et al (2019)). (H, I) The corresponding oncoprints showing no significant overlap between (H) patients with MAPK pathway mutations and high tumor mutational burden in this HNSCC-oral cancer cohort (TMB score 20% cutoff within HNSCC histology [N = 139] in the study by Samstein et al (2019)) and (I) no significant overlap for patients with MAPK pathway mutations and high tumor mutational burden in this HNSCC distant metastasis cohort (TMB score 20% cutoff within HNSCC histology).