Table 1.
Summary of Clinical Evidence Revealing TMB as a Biomarker for Response to Immunotherapy in Lung Cancer
| Immunotherapy Agent | Study/Trial | TMB Assay Used | Type of Benefit |
|---|---|---|---|
| Nivolumab | |||
| NSCLC (1L) | CheckMate 02631 | WES | ORR, PFS |
| NSCLC | Flatiron Health20 | Foundation CGP panel | OS |
| Nivolumab and ipilimumab combination | |||
| NSCLC (1L) | CheckMate 01249 | WES | ORR, DCB, PFS |
| NSCLC (1L) | CheckMate 22733 | FoundationOne CDx | ORR, PFS |
| NSCLC (1L) | CheckMate 56821 | FoundationOne CDx | ORR |
| SCLC (2L) | CheckMate 03222 | WES | ORR, OS, PFS |
| Pembrolizumab | |||
| NSCLC (1L) | Keynote-00130 | WES | ORR, DCB, PFS |
| Atezolizumab | |||
| NSCLC (2L) | POPLAR/OAK23,38 | Foundation bTMB | OS, PFS |
| NSCLC (2L) | POPLAR/FIR/BIRCH24 | FoundationOne | ORR, OS, PFS |
| NSCLC (1L) | BFAST and B-F1RST25, 26, 27 | Foundation bTMB | DOR, ORR, PFS, OS |
| NSCLC (1L) | Rizvi et al., 201861 | WES | DCB, ORR, PFS |
| Durvalumab | |||
| NSCLC (1L) | MYSTIC28,37 | FoundationOne CDx | OS |
| Durvalumab and tremelimumab combination | |||
| NSCLC (1L) | MYSTIC28,37 | FoundationOne CDx | OS |
| NSCLC (1L) | MYSTIC28,37 | Guardant OMNI bTMB | OS |
| Multiple Agents | |||
| NSCLC | Rozenblum et al., 201729 | FoundationOne Guardant 360 |
ORR |
| NSCLC | Samstein et al., 201915 | MSK-IMPACT | OS |
BFAST, Blood First Assay Screening Trial; B-F1RST, Blood First Line Ready Screening Tool; bTMB, blood tumor mutational burden; CGP, comprehensive genomic profiling; DCB, durable clinical benefit; DOR, duration of response; MSK-IMPACT, Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; TMB, tumor mutational burden; WES, whole-exome sequencing.
Adapted from Büttner et al.19