Table 1 Overview of the main published studies on TMB quantification from gene panels
From: Tumor mutational burden quantification from targeted gene panels: major advancements and challenges
Reference | Gene panel (version) | Cancer type | Study design | Study ID | ICI | TMB cutoff (mut/Mb) | Method of TMB cutoff determination | TMB predictive value | Clinical outcome | N patients |
|---|---|---|---|---|---|---|---|---|---|---|
Rosenberg, 2016 [5] | FM1 (v3) | urothelial carcinoma (metastatic or locally advanced) | trial (single-arm, phase 2) | NCT02108652 | PD-(L)1 | NA | NA | NA | ORR | 315 |
Balar, 2017 [16] | FM1± | urothelial carcinoma (metastatic) | trial (single-arm, phase 2) | NCT02108652 | PD-(L)1 | Q3 (> = 16) | distribution | NA | OS | 123 |
Powles, 2018 [15] | FM1± | urothelial carcinoma (metastatic) | trial (randomized, phase 3) | NCT02302807 | PD-(L)1 | Q2 (9.65) | distribution | NA | OS | 931 |
Kowanetz, 2016 [27] | FM1 (v3) | NSCLC | trial (randomized, phase 2) | NCT01903993 | PD-(L)1 | Q1, Q2 (9.9), Q3 | distribution | NA | PFS, OS, ORR | 454 |
trial (single-arm, phase 2) | NCT02031458 | |||||||||
trial (single-arm, phase 2) | NCT01846416 | |||||||||
Gandara, 2018 [61] a | FM1 bTMB assay | NSCLC | trial (randomized, phase 2) | NCT01903993 | PD-(L)1 | > = 14 | positive and negative percentage agreement with the orthogonally validated FM1 | NA | PFS, OS | 259 |
trial (randomized, phase 3) | NCT02008227 | |||||||||
Hellmann, 2018 [50] | FM1 CDx | NSCLC | trial (randomized, phase 3) | NCT02477826 | combo | > 10 | based on NCT02659059 | NA | PFS | 1004 |
Rizvi, 2018 [42] | MSK-IMPACT (v1, v2, v3) | NSCLC | trial (randomized, phase 1) | NCT01295827 | PD-(L)1 | Q2 (7.4) | distribution | AUC = 0.601 (DCB) | DCB, PFS | 240 |
Ready, 2019 [28] | FM1 CDx | NSCLC | trial (non-randomized, phase 2) | NCT02659059 | combo | 10 | ROC | AUC (95% CI) = 0.73 (0.62–0.84); TPR (95% CI) = 0.78 (0.63–0.93); FPR (95% CI) = (0.62 (0.49–0.73) | ORR | 98 |
Wang, 2019 [49] a | NCC-GP150 | NSCLC | observational (cohort) | NA | PD-(L)1 | 6 (tot mut) | best cutoff from in silico analysis on Rizvi 2015 WES | NA | PFS, ORR | 50 |
Johnson, 2016 [12] | FM1 (v2, v3) | melanoma | observational (retrospective) | NA | PD-(L)1 | < 3.3, 3.3–23.1, > 23.1 | ROC | NA | PFS, OS, ORR | 65 |
Chalmers, 2017 [22] | FM1 (v1, v2, v3, v4), FM1 Heme | various locally advanced or metastatic solid tumors | observational (retrospective) | NA | NA | > 20 | NA | NA | NA | 102, 292 |
Goodman, 2017 [18] | FM1 (v1, v2, v3) | various locally advanced or metastatic solid tumors | observational (cohort, retrospective) | NCT02478931 | PD-(L)1, CTLA-4, high-dose IL2 or combo | < 6, 6–19, > 19 | Foundation Medicine official reports | NA | PFS, OS, ORR | 151 |
Khagi, 2017 [44] a | Guardant360 | various solid tumors | observational (cohort, retrospective) | NCT02478931 | PD-(L)1, CTLA-4, combo or other | mean (> 3 VUS) | distribution | NA | PFS, OS, ORR | 69 |
Zehir, 2017 [73] | MSK-IMPACT (v1, v2) | various primary and metastatic solid tumors | observational (cohort, prospective) | NCT01775072 | NA | > 13.8 | distribution (median TMB +  2 × IQR_TMB) | NA | NA | 10, 945 |
Samstein 2019 [43] | MSK-IMPACT (v3) | bladder | observational (cohort, prospective) | NCT01775072 | PD-(L)1, CTLA-4 or combo | 17.6 | distribution (top 20%) | NA | OS, PFS, DCB | 214 |
breast | 5.9 | 45 | ||||||||
breast ER+ | 6.8 | 24 | ||||||||
breast ER- | 4.4 | 21 | ||||||||
unknown primary | 14.2 | 90 | ||||||||
colorectal | 52.2 | 110 | ||||||||
esophagogastric | 8.8 | 126 | ||||||||
glioma | 5.9 | 117 | ||||||||
head and neck | 10.3 | 138 | ||||||||
melanoma | 30.7 | 321 | ||||||||
NSCLC | 13.8 | 350 | ||||||||
renal cell carcinoma | 5.9 | 151 |