Table 2.
Clinical trials in terms of the predictive value of RAS mutational status to treatment response
| Study | No. Total | No. Mut | Tumor stage | Treat | OS (mon) | HR (95%CI) | P | PFS (mon) | HR (95%CI) | P | References |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Targeted therapy | |||||||||||
| Lievre, A., et al | 89 | 24 | mCRC | Cetuximab for KMP vs KWP | 10.1 vs 14.3 | ND | .026 | 2.4 vs 7.3 | ND | .0001 | [11] |
| NCT00079066 | 572 | 164 | mCRC | Cetuximab + BSC vs BSC For KMP | 4.5 vs 4.6 | 0.98 (0.70–1.37) | .89 | 1.8 vs 1.8 | 0.99 (0.73–1.35) | .96 | [211] |
| Amado, R. G., et al | 427 | 184 | mCRC | Panitumumab + BSC vs BSC For KMP | 4.9 vs 4.4 | 1.02 (0.75–1.39) | ND | 1.7 vs 1.7 | 0.99 (0.73–1.36) | ND | [212] |
| OPUS | 337 | 99 | mCRC | Cetuximab + FOLFOX4 vs FOLFOX4 for KMP | NA | ND | ND | 5.5 vs 8.6 | 1.83 (1.10–3.05) | .0192 | [213] |
| NCT00154102 | 1198 | 397 | mCRC | Cetuximab + FOLFIRI vs FOLFIRI for KMP | 16.2 vs 16.7 | 1.035 (0.834–1.284) | .75 | 7.4 vs 7.7 | 1.17 (.887–1.544) | .26 | [214] |
| NCT00364013 | 1096 | 440 | mCRC | Panitumumab + FOLFOX4 vs FOLFOX4 for KMP and NMP | 15.6 vs 19.2 | 1.25 (1.02–1.55) | .03 | 7.3 vs 8 | 1.31 (1.07–1.60) | ND | [41] |
| NCT00339183 | 1083 | 486 | mCRC | Panitumumab + FOLFIRI vs FOLFIRI for KMP | 11.8 vs 11.1 | ND | ND | 5.0 vs 4.9 | ND | .14 | [215] |
| NCT00145314 | 1064 | 195 | mCRCIV | Cetuximab + FLOX vs FLOX KMP for KMP | 21.1 vs 20.4 | 1.03 (0.68–1.57) | .89 | 9.2 vs 7.8 | 0.71 (0.50–1.03) | .07 | [216] |
| NCT01000025 | 720 | 78 | NSCLC IV | Dacomitinib vs placebo for KMP | 5.82 vs 8.28 | 2.10 (1.05–4.22) | NA | 1.61 vs 1.86 | 1.34 (0.78–2.29) | ND | [217] |
| NCT00637910 | 219 | 51 | NSCLC IV | Docetaxel vs Erlotinib for KMP | NA | 0.81 (0.45–1.47) | ND | NA | 0.89 (0.51–1.57) | ND | [218, 219] |
| TRIBUTE | 274 | 55 | NSCLC IIIB or IV | Erlotinib + CP vs CP for KMP | 4.4 vs 13.5 | NA | .019 | NA | ND | ND | [44] |
| TRUST | 311 | 17 | NSCLC IIIB or IV | Erlotinib for KMP vs KWP | NA | 1.64 (0.97–2.80) | .064 | NA | 1.56 (0.92–2.65) | .094 | [220] |
| NCIC CTG PA.3 | 569 | 92 | aPC | Erlotinib + Gem vs placebo + Gem for KMP | 6.0 vs 7.4 | 1.07 (0.68–1.66) | .78 | NA | ND | ND | [221, 222] |
| NCT00440167 | 281 | 121 | aPC | Gem + Erlotinib/Cap or Cap + Erlotinib/Gem for KWP vs KMP | 7.9 vs 5.7 | 1.68 (1.17–2.41) | .005 | NA | ND | ND | [223] |
| NCT01267344 | 122 | 44 | aBTC | Gem, Ox + Cetuximab vs Gem, Ox For KMP | NA | 0.73 (0.39–1.35) | .313 | NA | ND | ND | [224] |
| Chemotherapy | |||||||||||
| CALGB 89803 | 508 | 178 | CRC III | FU/LV or IFL for KMP vs KWP | NA | 0.86 (0.60–1.23) | ND | NA | 0.95 (0.70–1.28) | ND | [225] |
| TRIBUTE | 274 | 55 | NSCLC IIIB or IV | CP for KMP vs KWP | 13.5 vs 11.3 | ND | ND | NA | ND | ND | [44] |
| OPUS | 337 | 99 | mCRC | FOLFOX4 for KMP vs KWP | NA | ND | ND | 8.6 vs 7.2 | 1.404 (0.867–2.271) | ND | [213] |
KMP KRAS-mutant patients, NMP NRAS-mutant patients, KWP wild-type KRAS patients, BSC best supportive care, mCRC metastatic colorectal cancer, NSCLC non-small-cell lung carcinoma, aPC advanced pancreatic cancer, aBTC advanced biliary tract cancer, FOLFOX4 oxaliplatin, fluorouracil, and leucovorin, FOLFIRI 5-fluorouracil, folinic acid, and irinotecan, Gem gemcitabine, CP carboplatin and paclitaxel, Cap capecitabine, Ox oxaliplatin, IFL fluorouracil [5-FU], leucovorin, and irinotecan, FU/LV 5FU + leucovorin, NA none, ND not determined