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Falta de estandarización entre estudios y punto de corte
1L = first line; 2L = second line; bTMB = blood TMB; IQR = interquartile range; mut/Mb = mutations per megabase; NSCLC = non-small cell lung cancer;
SCLC = small cell lung cancer; TMB = tumor mutational burden; WES = whole exome sequencing. FoundationOne
®
covers 322 genes (and gene
rearrangements).
18
FoundationOne CDx
™
uses next-generation sequencing to detect substitutions, insertions and deletions, and copy number alterations in 324
genes and select gene rearrangements. References are in the slide notes.
36
Assay
Tumor type
Cutoff
Study/trial
MSK-IMPACT™
Multiple solid tumors
High: median TMB + 2*IQR TMB
Zehir, et al.
1
NSCLC
High: above vs below the 50th percentile of TMB
Rizvi, et al.
2
WES
1L NSCLC
Total missense mutations:
low 0 to <100; medium 100 to 242; high ≥243
CheckMate 026
3
1L NSCLC
Above and below median (158 mut) and quartiles
CheckMate 012
4
2L+ SCLC
Total missense mutations:
low 0 to <143; medium 143 to 247; high ≥248
CheckMate 032
5
2L+ bladder
Total missense mutations:
low 0 to <85; medium 85 to 166; high ≥167
CheckMate 275
6
Melanoma
100 mut/tumor
Snyder, et al.
7
1L or 2L+ melanoma
100 mut/tumor
CheckMate 038
8
1L+ NSCLC
200 ns mut/tumor
KEYNOTE-001
9
Advanced solid tumors
102 ns mut/tumor
KEYNOTE-012
10
FoundationOne
®
1L or 2L+ NSCLC
9.9 mut/Mb (median) or 16.2 mut/Mb (75% quartile)
FIR/BIRCH/POPLAR
11
1L bladder
0.9 to 62.2 mut/Mb (quartiles)
IMvigor 210
12
FoundationOne CDx™
1L NSCLC
≥10 mut/Mb
CheckMate 227
13
CheckMate 568
14
bTMB assay
1L NSCLC
≥12, ≥14, ≥16, ≥20
B-F1RST
15
2L+ NSCLC
≥10 (9 mut/Mb) or ≥16 (14 mut/Mb) or ≥20
POPLAR/OAK
16,17