Table 5. K-ras mutational analysis in randomised studies evaluating EGFR antibodies.
| Study | No. of patients evaluable for K-ras mutation/No. of patients in the ITT study population | Proportion of patients with K-ras mutations | Treatment by mutation status | Response rates (%) | P-value | Median progression-free survival | P-value | Median overall survival | P-value |
|---|---|---|---|---|---|---|---|---|---|
| First line | |||||||||
| Van Cutsem et al (2009) | 540/1198 (45%) | 35.6% mutant | Wild type | ||||||
| CRYSTAL | FOLFIRI | 43.2 | 0.0025 | 8.7 months | 0.02 | 21.0 months | HR: 0.84 (95% CI: 0.64–1.11) | ||
| FOLFIRI +cetuximab | 59.3 | 9.9 months | 24.9 months | ||||||
| Mutant | |||||||||
| FOLFIRI | 40.2 | 0.46 | 8.1 months | 0.75 | 17.7 months | HR: 1.03 (95% CI: 0.74–1.44) | |||
| FOLFIRI +cetuximab | 36.2 | 7.6 months | 17.5 months | ||||||
| Bokemeyer et al (2009) | 233/337 (69%) | 42% mutant | Wild type | ||||||
| OPUS | FOLFOX | 37 | 0.011 | 7.2 months | 0.0163 | NR | NR | ||
| FOLFOX +cetuximab | 61 | 7.7 months | NR | ||||||
| Mutant | |||||||||
| FOLFOX | 49 | 0.106 | 8.6 months | 0.0192 | NR | NR | |||
| FOLFOX +cetuximab | 33 | 5.5 months | NR | ||||||
| Hecht et al (2009) | 865/1053 (82%) | 40% mutant | Wild type | ||||||
| PACCE | FOLFOX + bevacizumab | 56 | NR | 11.5 months | HR: 1.36 (95% CI: 1.04–1.77) | 24.5 | 0.045 | ||
| FOLFOX + bevacizumab + panitumumab | 50 | 9.8 months | 20.7 | ||||||
| Mutant | |||||||||
| FOLFOX + bevacizumab | 44 | NR | 11.0 months | 19.3 | |||||
| FOLFOX + bevacizumab + panitumumab | 47 | 10.4 months | 19.3 | ||||||
| Tol et al (2009) | 528/736 (72%) | 39.6% mutant | Wild type | ||||||
| CAIRO 2 | CAPOX + bevacizumab | 50.0 | 0.06 | 10.6 months | 0.030 | 22.4 months | 0.64 | ||
| CAPOX + bevacizumab +cetuximab | 61.4 | 10.5 months | 21.8 months | ||||||
| Mutant | |||||||||
| CAPOX + bevacizumab | 59.2 | 0.03 | 12.5 months | 0.003 | 24.9 months | 0.03 | |||
| CAPOX + bevacizumab +cetuximab | 45.9 | 8.1 months | 17.2 months | ||||||
| Hecht et al (2009) | 865/1053 (82%) | 40% mutant | Wild type | ||||||
| PACCE | FOLFIRI + bevacizumab | 48 | NR | 12.5 months | NR | 19.8 | NR | ||
| FOLFIRI + bevacizumab + panitumumab | 54 | 10.0 months | NE | ||||||
| Mutant | |||||||||
| FOLFIRI + bevacizumab | 38 | NR | 11.9 months | 20.5 months | |||||
| FOLFIRI + bevacizumab + panitumumab | 30 | 8.3 months | 17.8 months | ||||||
| Subsequent lines | |||||||||
| Tejpar et al (2008) | 148/157 (94%) | 39% mutant | Wild type | ||||||
| EVEREST | Irinotecan +cetuximab (standard dose) | 30.4 | 0.396 | 5.7 months for all wild-type patients | 0.014 (in favour of wild type in standard dose) | NR | NR | ||
| Irinotecan +cetuximab (escalating dose) | 41.9 | NR | |||||||
| Mutant | <0.0001 | ||||||||
| Irinotecan +cetuximab (standard dose) | 0 | NR | 2.7 months for all mutant patients | (in favour of wild type in escalating dose) | NR | NR | |||
| Irinotecan +cetuximab (escalating dose) | 0 | NR | |||||||
| Amado et al (2008) | 427/463 (92%) | 43% mutant | Wild type | ||||||
| Panitumumab | 17 | NR | 12.3 weeks | <0.0001 | 8.1 months | NS | |||
| BSC | 0 | 7.3 weeks | 7.6 months | ||||||
| Mutant | |||||||||
| Panitumumab | 0 | NR | 7.4 weeks | 0.99 | 4.9 months | NS | |||
| BSC | 0 | 7.3 weeks | 4.4 months | ||||||
| Karapetis et al (2008) | 394/572 (69%) | 42.3% mutant | Wild type | ||||||
| NCIC CO.17 | Cetuximab | 12.8 | NR | 3.7 months | <0.001 | 9.5 months | <0.00 | ||
| BSC | 0 | 1.9 months | 4.8 months | 1 | |||||
| Mutant | |||||||||
| Cetuximab | 1.2 | NR | 1.8 months | 0.96 | 4.5 months | 0.89 | |||
| BSC | 0 | 1.8 months | 4.6 months | ||||||
ITT=intension to treat; FOLFOX=oxaliplatin-infused 5-FU/LV; FOLFIRI=irinotecan-infused 5-FU/LV; BSC=best supportive care; NR=not reported; NS=not significant; NE=not estimable.