Table 2.
RAS mutational status as a predictor of response and survival with anti-EGFR therapy.
| Study | RAS status | n | Treatment | RR |
PFS |
OS |
|||
|---|---|---|---|---|---|---|---|---|---|
| % | p value* | Median (months) | p value* | Median (months) | p value* | ||||
| CALGB/SWOG 80405 ESMO [2014], Lenz et al. [2014], Venook et al. [2014] |
KRAS wt exon 2 | 559 | (FOLFOX or FOLFIRI)/bevacizumab | NA | NA | 10.84 | 0.55 | 29.0 | 0.34 |
| 578 | (FOLFOX or FOLFIRI)/cetuximab | 10.45 | 29.9 | ||||||
| RAS wt at all loci | 256 | (FOLFOX or FOLFIRI)/bevacizumab | 53.6 | <0.01 | NA | NA | 31.2 | 0.40 | |
| 270 | (FOLFOX or FOLFIRI)/cetuximab | 68.6 | NA | 32.0 | |||||
| European consortium De Roock et al. [2010] |
KRAS mut exon 2, 3, 4 | 253 | Chemotherapy/cetuximab | 6.7 | <0.0001 | 2.8 | <0.0001 | 7.4 | <0.0001 |
| KRAS wt exon 2, 3, 4 | 352 | 35.8 | 5.5 | 11.5 | |||||
| NRAS mut exon 2, 3, 4 | 13 | Chemotherapy/cetuximab | 7.7 | 0.013 | 3.5 | 0.055 | 8.8 | 0.051 | |
| NRAS wt exon 2, 3, 4 | 289 | 38.1 | 6.5 | 11.5 | |||||
| OPUS Bokemeyer et al. [2011], Tejpar et al. [2014] |
KRAS wt exon 2 | 82 | FOLFOX4/cetuximab | 57 | 0.0027 | 8.3 | 0.0064 | 22.8 | 0.39 |
| 97 | FOLFOX4 | 34 | 7.2 | 18.5 | |||||
| KRAS mut exon 2 | 77 | FOLFOX4/cetuximab | 34 | 0.0290 | 5.5 | 0.015 | 13.4 | 0.20 | |
| 59 | FOLFOX4 | 53 | 8.6 | 17.5 | |||||
| KRAS mut exon 3, 4 | 17 | FOLFOX4/cetuximab | 47.1 | 0.57 | 7.3 | 0.96 | 14.8 | 0.41 | |
| NRAS mut exon 2, 3, 4 | 19 | FOLFOX4 | 36.8 | 7.4 | 17.8 | ||||
| RAS mut at any exon | 94 | FOLFOX4/cetuximab | 36.2 | 0.11 | 5.6 | 0.018 | 13.4 | 0.089 | |
| 78 | FOLFOX4 | 48.7 | 7.8 | 17.8 | |||||
| RAS wt at all exon | 36 | FOLFOX4/cetuximab | 61.1 | 0.008 | 12 | 0.018 | 20.7 | 0.50 | |
| 46 | FOLFOX4 | 30.4 | 5.8 | 17.8 | |||||
| CRYSTAL Van Cutsem et al. [2015] |
KRAS mut exon 3, 4 | 32 | FOLFIRI/cetuximab | 34.4 | 0.97 | 7.2 | 0.56 | 18.2 | 0.50 |
| NRAS mut exon 2, 3, 4 | 31 | FOLFIRI | 35.5 | 6.9 | 20.7 | ||||
| RAS mut at any exon | 246 | FOLFIRI/cetuximab | 31.7 | 0.40 | 7.4 | 0.47 | 16.4 | 0.64 | |
| 214 | FOLFIRI | 36 | 7.5 | 17.7 | |||||
| RAS wt at all loci | 178 | FOLFIRI/cetuximab | 66.3 | <0.0001 | 11.4 | 0.0002 | 28.4 | 0.0024 | |
| 189 | FOLFIRI | 38.6 | 8.4 | 20.2 | |||||
| 20050181 Peeters et al. [2014] |
RAS mut at any loci | 299 | FOLFIRI/panitumumab | NA | NA | 4.8 | 0.14 | 11.8 | 0.34 |
| 294 | FOLFIRI | 4.0 | 11.1 | ||||||
| RAS wt at all loci | 208 | FOLFIRI/panitumumab | NA | NA | 6.4 | 0.007 | 16.2 | 0.08 | |
| 213 | FOLFIRI | 4.6 | 13.9 | ||||||
| PRIME Douillard et al. [2013] |
KRAS wt exon 2 with other RAS mut |
51 | FOLFOX4/panitumumab | NA | NA | 7.3 | 0.33 | 17.1 | 0.12 |
| 57 | FOLFOX4 | 8.0 | 17.8 | ||||||
| RAS mut at any loci | 272 | FOLFOX4/panitumumab | NA | NA | 7.3 | 0.008 | 15.5 | 0.001 | |
| 276 | FOLFOX4 | 8.7 | 18.7 | ||||||
| RAS wt at all loci | 259 | FOLFOX4/panitumumab | NA | NA | 10.1 | 0.004 | 25.8 | 0.009 | |
| 253 | FOLFOX4 | 7.9 | 20.2 | ||||||
| PLANET Abad et al. [2014] |
KRAS wt exon 2 | 38 | FOLFOX4/panitumumab | 73.7 | NA | 12.5 | 0.943 | 32.5 | 0.848 |
| 39 | FOLFIRI/panitumumab | 66.7 | 12.6 | 42.4 | |||||
| RAS mut in any foci | NA | FOLFOX4/panitumumab | 50.0 | NA | NA | NA | NA | NA | |
| NA | FOLFIRI/panitumumab | 57.1 | |||||||
| RAS wt at all loci | NA | FOLFOX4/panitumumab | 77.8 | NA | 12.8 | 0.621 | 39.0 | 0.935 | |
| NA | FOLFIRI/panitumumab | 73.1 | 14.8 | 45.8 | |||||
| PEAK Schwartzberg et al. [2014] |
KRAS wt exon 2 | 142 | mFOLFOX6/panitumumab | NA | NA | 10.9 | 0.353 | 34.2 | 0.009 |
| 143 | mFOLFOX6/bevacizumab | 10.1 | 24.3 | ||||||
| RAS wt at all loci | 88 | mFOLFOX6/panitumumab | NA | NA | 13 | 0.029 | 41.3 | 0.058 | |
| 82 | mFOLFOX6/bevacizumab | 9.5 | 28.9 | ||||||
*
Compared to row immediately below. EGFR, epidermal growth factor receptor; mut, mutation; NA, not available; OS, overall survival; PFS, progression-free survival; RR, relative risk; wt, wildtype.