Table 1.
Clinical and Genomic Characteristics of ERBB2‐ and ERBB3‐mutated mCRC
| All mCRC | ERBB2 Positive | ERBB2 Positive | ERBB3 Positive | Cooccurring ERBB2/3 | ||
|---|---|---|---|---|---|---|
| Amplification | Short Variants | Amp + SV | ||||
| No. of cases | ||||||
| Total | 8887 | 251 (2.8%) | 135 (1.5%) | 35 (0.4%) | 140 (1.6%) | 8 (0.1%) |
| Colonic CRC | 7599 | 215 (2.8%) | 112 (1.5%) | 28 (0.4%) | 113 (1.5%) | 7 (0.1%) |
| Rectal CRC | 1288 | 36 (2.8%) | 23 (1.8%) | 7 (0.5%) | 27 (2.1%) | 1 (<0.1%) |
| Sample site | ||||||
| Colorectal | 4660 | 124 | 79 | 21 | 64 | 4 |
| Distant | 4176 | 124 | 55 | 14 | 74 | 4 |
| Stage | ||||||
| IV | 100% | 100% | 100% | 100% | 100% | 100% |
| Patient demographics | ||||||
| Median age (range), y | 56 (8‐96) | 54 (22‐88) | 59 (31‐79) | 57 (29‐87) | 54 (14‐83) | 53 (46‐80) |
| Sex | ||||||
| Female | 45% | 43% | 41% | 46% | 39% | 50% |
| Male | 55% | 57% | 59% | 54% | 60% | 50% |
| ERBB mutation type | ||||||
| Amplification | NA | 251 | ‐ | ‐ | 2 | 0 |
| Short variant | NA | ‐ | 135 | ‐ | 138 | 8 |
| Amp + SV | NA | ‐ | ‐ | 35 | 0 | 0 |
| Global mutation metrics | ||||||
| TMB (mut/Mb) | ||||||
| Range | 0‐854.1 | 0‐230.6 | 0‐230.6 | 0‐10.1 | 0‐854.1 | 6.3‐126.1 |
| Median | 3.8 | 3.6 | 5.4 | 3.8 | 5.4 | 44.2 |
| <6 mut/Mb | 6294 (70.8%) | 179 (71.3%) | 68 (50.4%) | 27 (77.1%) | 79 (56.4%) | 0 (0.0%) |
| 6‐20 mut/Mb | 2173 (24.5%) | 72 (28.7%) | 38 (28.1%) | 8 (22.9%) | 36 (25.7%) | 2 (25.0%) |
| ≥20 mut/Mb | 420 (4.7%) | 0 (0%) | 29 (21.5%) | 0 (0%) | 25 (17.9%) | 6 (75.0%) |
| P | ‐ | <<.0005 | <.0001 | NS | <<.0001 | <<.0001 |
| MSI | ||||||
| No. of cases evaluated | 5899 | 171 | 77 | 24 | 83 | 5 |
| Stable | 5389 (91.4%) | 169 (98.8%) | 64 (83.1%) | 24 (100%) | 69 (83.1%) | 1 (20%) |
| Ambiguous | 103 (1.7%) | 2 (1.2%) | 1 (1.3%) | 0 (0%) | 1 (1.2%) | 1 (20%) |
| High | 407 (6.9%) | 0 (0%) | 12 (15.6%) | 0 (0%) | 12 (14.5%) | 3 (60%) |
| P | ‐ | <.005 | <.005 | NS | <.05 | <<.0001 |
Abbreviations: Amp, amplification; mCRC, metastatic colorectal cancer; MSI, microsatellite instability; NA, not applicable, NS, not significant; mut/Mb, mutations per megabase; TMB, tumor mutational burden; SV, short variant.
Samples in the cooccurring column had both ERBB2 and ERBB3 alterations, whereas other samples had only ERBB2 or ERBB3 alterations. Sample site was defined as colorectal for the colon or rectum and distant for all others; a subset of samples did not have the exact sample site defined. Significance values for TMB and MSI were calculated by the chi‐square test and compared the distribution of samples positive for a given alteration type with the distribution for all other samples in the data set.