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.