Table 1.
KRAS and treatment response to Cetuximab or Panitumumab in previously treatment patients with colorectal cancer.
| Study | Treatments | KRAS | N (%) | RR, N (%) | TTP (months) | OS (months) | Remarks |
| Cetuximab Studies | |||||||
| Moroni, 2005 | CTX = 12 | WT | 16 | 6 (38%) | NA | NA | KRAS MT has worse RR. |
| CTX + IRI = 9 | MT | 5 (24%) | 0 (0%) | NA | NA | ||
| Lievre, 2006a | CTX = 1 | WT | 17 | 11 (36.7%) | NA | 16.3 | KRAS MT has worse RR and OS. |
| CTX + IRI = 25 | MT | 13 (43.3%) | 0 | NA | 6.9 | ||
| CTX + FOLFIRI = 4 | |||||||
| Benvenuti, 2007 | CTX = 12 | WT | 32 | 10 (31.3%) | NAb | NA | KRAS MT has worse RR and TTP.b |
| CTX + IRI = 11 | MT | 16 (33.3%) | 1 (6.3%) | NAb | NA | ||
| Finocchiaro, 2007 | CTX = 5 | WT | 49 | 13 (26.5%) | 6.1 | 10.8 | KRAS MT has worse RR, TTP, and OS. |
| CTX + IRI = 77 | MT | 32 (39.5%) | 2 (6.3%) | 3.7 | 8.3 | ||
| CTX + OX = 3 | |||||||
| Di Fiore, 2007 | CTX + IRI/OX | WT | 37 | 12 (32.4%) | 5.5 | NA | KRAS MT has worse RR and TTP. |
| MT | 22 (37.3%) | 0 | 3.o | NA | |||
| Khambata-Ford, 2007 | CTX | WT | 50 | 6 (12%) | 2.0 | NA | KRAS MT has worse RR. |
| MT | 30 (37.5%) | 0 | 2.0 | NA | |||
| Lievre, 2008a | CTX = 2 | WT | 65 | 26 (40.0%) | 7.9 | 14.3 | KRAS MT has worse RR, TTP, and OS. |
| CTX + IRI = 78 | MT | 24 (27.0%) | 0 | 2.5 | 10.1 | ||
| CTX + FOLFIRI = 9 | |||||||
| DeRoock, 2008 | CTX = 30 | WT | 67 | 27 (40.9%) | 6.0 | 10.8 | KRAS MT has worse RR, TTP, and OS. |
| CTX + IRI = 83 | MT | 46 (40.7%) | 0 | 3.0 | 6.8 | ||
| Tejpar, et al. 2008 | CTX + IRI | WT | 62 | NA | NA | 11.5 | KRAS WT has worse OS. |
| MT | 33 (35%) | NA | NA | 4.2 | |||
| Stoehlmacher, 2008 | CTX + IRI/OX | WT | 22 | NA | NA | NA | KRAS WT did not respond. |
| MT | 8 (26%) | 0 | NA | NA | |||
| Tejpar, et al. 2008a | IRI + CTX standard dose | WT | 23 | 7 (30.4%) | NA | NA | KRAS MT has worse RR. |
| MT | 20 (44.4%) | 0 | NA | NA | |||
| IRI + CTX escalated dose | WT | 31 | 13 (41.9%) | NA | NA | Escalated dose did not overcome KRAS MT. | |
| MT | 12 (27.3%) | 0 | NA | NA | |||
| Karapetis, et al. 2008 | CTX | WT | 117 | 15 (12.8%) | 3.7 | 9.5 | CTX also improved quality of life in KRAS WT patients. |
| MT | 81 (40.9%) | 1 (1.2%) | 1.8 | 4.5 | |||
| BSC | WT | 113 | NA | 1.9 | 4.8 | ||
| MT | 83 (42.3%) | NA | 1.8 | 4.6 | |||
| Panitumumab Studies | |||||||
| Moroni, 2005 | PAN | WT | 5 | 2 (40%) | NA | NA | KRAS MT did not have impact on response. |
| MT | 5 (50%) | 2 (40%) | NA | NA | |||
| Benvenuti, 2007 | PAN | WT | 15 | 3 (20%) | NAb | NA | KRAS MT has worse RR and TTP.b |
| MT | 10 | 1 (10%) | NAb | NA | |||
| Amado, 2008 | PAN | WT | 124 | 21 (16.9%) | 3.1 | 8.1 | KRAS MT has worse RR, TTP, and OS. |
| MT | 84 (40.4%) | 0 | 1.9 | 4.9 | |||
| BSC | WT | 119 | 0 | 1.8 | 7.6 | ||
| MT | 100 (45.7%) | 0 | 1.8 | 4.4 | |||
| Freeman, 2008 | PAN | WT | 38 | 4 (10.5%) | 4.1 | 10.7 | KRAS MT has worse RR, TTP, and OS. |
| MT | 24 (38.7%) | 0 | 1.9 | 5.6 |
a The 2006 and 2008 studies by Lievre and coworkers were based on independent patient series.
b For all patients (CTX and PAN), average TTP was 3.7 months for patients with wild type KRAS versus 1.7 months for patients with mutant KRAS.
Abbreviations: CTX = cetuximab; PAN = panitumumab; IRI = irinotecan; Ox = oxaliplatin; Cap = capcitabine; BSC = best supportive care; WT = wild type; MT = mutant-type; RR = objective response rate (complete response + partial response); TTP = time to progression, OS = overall survival; NA = Not Available or Not Applicable.