Table 1.
Main randomized clinical trials in first-line treatment for patients with metastatic colorectal cancer (mCRC).
| Author, Journal Year (ref) | N | Treatments | HR PFS/OS < 0.8 | Adequate Control Arm | PFS Censored <20% at 2y |
Any Change in Primary End- Point or Sample |
Achieved Pre- Specified Objective |
Quality Design | ESMO/MCBS 1.1 |
|---|---|---|---|---|---|---|---|---|---|
| Bevacizumab vs. no bevacizumab | |||||||||
| Kabbinavar F, JCO 2003 [6] | 104 | bev plus FU vs. FU | 0.54/0.86. 0.62 | no | NA | no | NA | 2 of 5 | 1 of 3 |
| Kabbinavar FF, JCO 2005 [7] | 209 | bev plus FU vs. FU | 0.5/0.79. 0.63 | no | yes | no | no | 3 of 5 | 0 of 3 |
| Hurwitz H, NEJM 2004 [8] | 813 | bev plus IFL vs. IFL | 0.54/0.66. 0.95 | yes | yes | no | yes | 4 of 5 | 2 of 3 |
| Saltz LB, JCO 2008 [9] | 1401 | bev plus FOLFOX/CAPOX vs FOLFOX/CAPOX |
0.83/0.89.0.93 | yes | yes | no | no | 3 of 5 | 0 of 3 |
| Tebbutt NC, JCO 2010 [10] | 471 | bev plus cap or cap/mit vs. cap or cap/mit |
0.61/0.86. 0.71 | no | yes | no | yes | 4 of 5 | 0 of 3 |
| Stathopoulos GP, Oncology 2010 [11] | 222 | bev plus IFL vs. IFL | NA | no | NA | no | NA | 1 of 5 | 0 of 3 |
| Guan ZZ, Chin J Cancer 2011 [12] | 214 | bev plus IFL vs. IFL | 0.44/0.62. 0.71 | no | yes | NA | NA | 2 of 5 | 2 of 3 |
| Pasardi A, Ann Oncol 2015 [13] | 376 | bev plus FOLFIRI or FOLFOX vs FOLFIRI or FOLFOX |
0.86/1.13. 0.76 | yes | yes | yes | no | 3 of 5 | 0 of 3 |
| Loupakis F, NEJM 2014 [14] | 508 | bev plus FOLFOXIRI vs. FOLFIRI | 0.75/0.79. 0.94 | yes | yes | no | yes | 4 of 5 | 0 of 3 |
| Anti-EGFR vs. no anti-EGFR in RAS WT | |||||||||
| Van Cutsem E, JCO 2015 [15] | 430/1198 | cet plus FOLFIRI vs. FOLFIRI | 0.56/0.69. 0.81 | yes | no | yes | no | 1 of 5 | 3 of 3 |
| Maugham TS, Lancet 2011 [16] | 729/1630 | cet plus FOLFOX or CAPOX vs FOLFOX or CAPOX |
0.96/1.04. 0.92 | yes | yes | yes | no | 2 of 5 | 0 of 3 |
| Tveit KM, JCO 2012 [17] | 274/571 | cet plus FLOX vs. FLOX | 1.07/1.14. 0.93 | no | yes | yes | no | 1 of 5 | 0 of 3 |
| Douillard JY, NEJM 2013 [18] | 512/1183 | pani plus FOLFOX vs. FOLFOX | 0.72/0.78. 0.92 | yes | no | yes | no | 1 of 5 | 2 of 3 |
| Bokemeyer C, Eur J Cancer 2015 [19] | 87/297 | cet plus FOLFOX vs. FOLFOX | 0.53/0.94. 0.56 | yes | yes | yes | no | 3 of 5 | 0 of 3 |
| Qin S, JCO 2018 [20] | 393 | cet plus FOLFOX vs. FOLFOX | 0.69/0.76. 0.91 | yes | yes | yes | no | 2 of 5 | 1 of 3 |
| Anti-EGFR vs. bevacizumab in RAS WT | |||||||||
| Venook AP, JAMA 2017 [21] | 474/1137 | bev plus FOLFOX or FOLFIRI vs cet plus FOLFOX or FOLFIRI |
1.03/0.83. 1.24 | yes | NA | yes | NA | 1 of 5 | 1 of 3 |
| Heinemann V, Lancet Onol 2014 [22] | 342/592 | bev plus FOLFIRI vs. cet plus FOLFIRI |
0.93/0.7. 1.32 | yes | NA | yes | NA | 1 of 5 | 3 of 3 |
| Schwartzberg LS, JCO 2014 [23] | 170/283 | bev plus FOLFOX vs. pani plus FOLFOX |
0.65/0.62. 1.04 | yes | yes | yes | NA | 2 of 5 | 3 of 3 |
| Triplets vs. doublets | |||||||||
| Souglakos J, Br J Cancer 2006 [24] | 283 | FOLFIRI vs. FOLFOXIRI | 0.83/NA | no | yes | no | no | 2 of 5 | 0 of 3 |
| Falcone A, JCO 2007 [25] | 244 | FOLFOXIRI vs. FOLFIRI | 0.63/0.7. 0.9 | no | yes | no | yes | 3 of 5 | 2 of 3 |
| Loupakis F, NEJM 2014 [14] | 508 | bev plus FOLFOXIRI vs. FOLFIRI | 0.75/0.79. 0.94 | yes | yes | no | yes | 4 of 5 | 0 of 3 |
| Sastre J, JCO 2019 [26] | 349 | Bev plus FOLFOX vs. bev plus FOLFOXIRI |
0.64/0.84. 0.76 | yes | NA | no | yes | 3 of 5 | 1 of 3 |
| Cremolini C, Lancet Oncol 2020 [27] | 679 | bev plus FOLFOX the bev plus FOLFIRI vs. bev plus FOLFOXIRI then bev plus FOLFOXIRI |
0.79/0.82. 0.96 | yes | yes | no | yes | 3 of 5 | 1 of 3 |
HR: hazard ratio, PFS: progression-free survival, OS: overall survival, NA: not available, ESMO/MCBS 1.1: European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1. [28].