Table 1.
Demographics, clinical characteristics, and outcomes in different cohorts
| KRAS G12C mutation (n = 238) | KRAS non-G12C mutation (n = 2947) | RAS/BRAF WT (n = 2249) | mCRC (N = 6477) | |
|---|---|---|---|---|
| Age at metastatic diagnosis, median (range), y | 59 (30-84) | 60 (20-85) | 58 (22-85) | 60 (18-85) |
| Female, n (%) | 103 (43.3) | 1443 (49.0) | 892 (39.7) | 2986 (46.1) |
| Race, n (%) | ||||
| White | 151 (63.4) | 1987 (67.4) | 1464 (65.1) | 4318 (66.7) |
| Black | 21 (8.8) | 278 (9.4) | 152 (6.8) | 503 (7.8) |
| Other | 48 (20.2) | 455 (15.4) | 473 (21.0) | 1173 (18.1) |
| NA | 18 (7.6) | 227 (7.7) | 160 (7.1) | 483 (7.5) |
| Community setting | 213 (89.5) | 2603 (88.3) | 2037 (90.6) | 5770 (89.1) |
| Diagnosed with metastatic disease in 2017 or later | 127 (53.4) | 1513 (51.3) | 1132 (50.3) | 3333 (51.5) |
| Metastatic disease at initial diagnosis | 135 (56.7) | 1710 (58.0) | 1290 (57.4) | 3739 (57.7) |
| Site of disease | ||||
| Colon | 163 (68.5) | 2171 (73.7) | 1610 (71.6) | 4743 (73.2) |
| Rectum | 71 (29.8) | 727 (24.7) | 588 (26.1) | 1606 (24.8) |
| Colorectal, NOS | 4 (1.7) | 49 (1.7) | 51 (2.3) | 128 (2.0) |
| Tumor sidednessa | ||||
| Left | 131 (55.0) | 1410 (47.8) | 1428 (63.5) | 3384 (52.2) |
| Right | 65 (27.3) | 880 (29.9) | 336 (14.9) | 1635 (25.2) |
| Other/unknown | 42 (17.6) | 657 (22.3) | 485 (21.6) | 1458 (22.5) |
| Mutation rates, n/Nb (%) | ||||
| APC | 197/233 (84.5) | 2458/2895 (84.9) | 1795/2198 (81.7) | 4967/6341 (78.3) |
| TP53 | 178/238 (74.8) | 1984/2947 (67.3) | 1933/2249 (85.9) | 4851/6477 (74.9) |
| PIK3CA | 40/238 (16.8) | 701/2947 (23.8) | 252/2249 (11.2) | 1156/6477 (17.8) |
| SMAD4 | 31/233 (13.3) | 413/2895 (14.3) | 167/2198 (7.6) | 734/6341 (11.6) |
| FBXW7 | 29/233 (12.4) | 331/2895 (11.4) | 151/2198 (6.9) | 608/6341 (9.6) |
| ATM | 10/233 (4.3) | 144/2895 (5.0) | 100/2198 (4.5) | 309/6341 (4.9) |
| HER2 | 1/238 (0.4) | 52/2947 (1.8) | 70/2249 (3.1) | 144/6477 (2.2) |
| PTEN | 14/238 (5.9) | 151/2947 (5.1) | 53/2249 (2.4) | 283/6477 (4.4) |
| BRAF | 4/238 (1.7) | 40/2947 (1.4) | 0/2249 (0) | 596/6477 (9.2) |
| BRAF V600E | 3/238 (1.3) | 4/2947 (0.1) | 0/2249 (0) | 443/6477 (6.8) |
| NRAS | 3/238 (1.3) | 26/2947 (0.9) | 0/2249 (0) | 289/6477 (4.5) |
| MET | 0/238 | 4/2947 (0.1) | 25/2249 (1.1) | 7/6477 (0.1) |
| NTRK | 0/233 | 3/2895 (0.1) | 9/2198 (0.4) | 14/6341 (0.2) |
| dMMR/MSI-H status, n/Nc (%) | ||||
| dMMR/MSI-H | 3/191 (1.6) | 70/2422 (2.9) | 62/1875 (3.3) | 236/5295 (4.5) |
| Not dMMR/MSI-H | 188/191 (98.4) | 2352/2422 (97.1) | 1813/1875 (96.7) | 5059/5295 (95.5) |
| Tumor mutational burden, n/Nc (%) | ||||
| <10 mutations/Mb | 210/223 (94.2) | 2643/2796 (94.5) | 1934/2056 (94.1) | 5638/6070 (92.9) |
| ≥10 mutations/Mb | 13/223 (5.8) | 153/2796 (5.5) | 122/2056 (5.9) | 432/6070 (7.1) |
| PD-L1 expression, n/Nc (%) | ||||
| <1% | 38/40 (95.0) | 501/555 (90.3) | 420/445 (94.3) | 1121/1237 (90.6) |
| 1%-49% | 2/40 (5.0) | 50/555 (9.0) | 22/445 (5.0) | 102/1237 (8.2) |
| ≥50% | 0/40 | 4/555 (0.7) | 3/445 (0.7) | 14/1237 (1.1) |
Left includes splenic flexure, descending colon, sigmoid, rectosigmoid junction, rectum; right includes cecum, ascending colon, hepatic flexure, transverse colon.
Data not available for all patients.
Includes subset of patients for whom data were available/testing was completed.
Abbreviations: APC, adenomatous polyposis coli; ATM, ATM serine/threonine kinase; BRAF, B-Raf proto-oncogene; CRC, colorectal cancer; FBXW7, F-box and WD repeat domain containing 7; HER2, human epidermal growth factor receptor 2; KRAS, Kirsten rat sarcoma viral oncogene homolog; Mb, megabase; MET, mesenchymal-epithelial transition; dMMR/MSI-H, deficient mismatch repair/microsatellite-high; NOS, not otherwise specified; NRAS, neuroblastoma RAS viral oncogene homolog; NTRK, neurotrophic tyrosine kinase gene; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PD-1/L1, programmed cell death-1/programmed death ligand-1; PTEN, phosphatase and tensin homolog deleted on chromosome 10; RAS, viral oncogene homolog; RAS/BRAF WT, RAS/BRAF WT mCRC cohort; SMAD4, Mothers Against Decapentaplegic homolog 4; TP53, tumor protein p53 gene; WT, wild-type.