Tumor mutational burden (TMB) demonstrates a positive association with clinical outcomes with pembrolizumab in gastric cancer

The association of tissue tumor mutational burden (tTMB) using the Foundation Medicine genomic platform with efficacy of pembrolizumab versus paclitaxel in patients (pts) with gastric cancer (GC) from KEYNOTE-061.

Abstract No : 4537

Abstract Type : Poster Discussion Session

Indication : Gastric cancer (GC)

Intervention : Pembrolizumab

Company : Merck & Co.

Technology : Tumor Mutational Burden (TMB)


tTMB was positively associated with ORR (P , 0.001; AUROC, 0.68), PFS (P , 0.001), and OS (P = 0.003) with pembrolizumab but not paclitaxel (ORR, P = 0.047; AUROC, 0.30; PFS, P = 0.605; OS, P = 0.084). Pt outcomes by tTMB cutoff are reported in the Table; prevalence of TMB $10 mut/Mb was 17%. In pts with microsatellite stable disease-only, HRs (95% CI) by treatment arm for OS by F1CDx cutoff were 0.40 (0.14-1.17) for tTMB $10 mut/Mb (n = 21) vs 0.97 (0.70-1.34) for tTMB ,10 mut/Mb (n = 168).


In this exploratory analysis from KEYNOTE-061, tTMB as determined by F1CDx demonstrated a positive association with clinical outcomes with pembrolizumab, but not paclitaxel, in pts with GC; these findings are consistent with those reported with whole exome sequencing. Pembrolizumab demonstrated an OS benefit vs paclitaxel in the subgroup with tTMB >10 mut/Mb, which remained when pts with microsatellite instability-high disease were excluded.


Tumor mutational burden (tTMB) demonstrated a positive association with clinical outcomes (i.e. in ORR and OS) with pembrolizumab in gastric cancer.

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