Table 1.

Studies in favor of using TMB as an agnostic biomarker for predicting response to immunotherapy.

Clinical Trial/Study	Cancer Type and Studied Therapy	Outcome Measure	In favor of TMB-H	References
Frameshift events predict anti-PD-1/L1 response in head and neck cancer (Hanna et al.)	– Head and neck cancer – Anti – PD-1/L1	Median OS among virus-negative patients	TMB-H (>10) > TMB-L (<5) OS = 20 months > OS = 6 months, respectively	[6]
AtezoTRIBE	– Metastatic colorectal cancer – FOLFOXIRI + Bevacizumab ± Atezolizumab	Median PFS	TMB-H (13.1 months) > TMB-L (11.5 months)	[7]
Keynote 158	– Advanced (unresectable and/or metastatic) solid tumors – Pembrolizumab monotherapy	ORR	TMB-H (ORR = 29%) > TMB-L (ORR = 6%)	[8]
Assessment of Tumor Mutational Burden and Outcomes in Patients With Diverse Advanced Cancers Treated With Immunotherapy (Aggarwal et al.)	– Solid tumors (NSCLC, bladder, head and neck squamous cell cancer …) – Anti-PD-1/PD-L1 ± anti-CTLA-4	OS	TMB-H > TMB-L [HR = 0.72] Prospective subgroup (TMB status evaluated pre ICI administration) TMB-H > TMB-L [HR, 0.61]	[9]
Checkmate 227	– Stage IV NSCLC – Nivolumab + Ipilimumab vs Nivolumab monotherapy or chemotherapy alone	PFS	Nivo + Ipi: TMB-H (7.2 months) > TMB-L (3.2 months)	[10]