Table 1.
Main results of trials evaluating triplet chemotherapy alone, in combination with bevacizumab or with anti-EGFRs
| Author | Phase | Primary endpoint |
Regimen | N | Response rate (%) |
Odds Ratio P-value |
Progression-free survival (95%CI) (months) |
HR P-value |
Overall survival (95%CI) (months) |
HR P-value |
R0 resection rate (%) |
R0 resection rate in pts with LLD (%) |
Relapse-free survival (months) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Falcone A, et al. 2007 | III | RR | FOLFOXIRI FOLFIRI |
122 122 |
66 41 |
P=0.0002 | 9.8 6.9 |
0.63 P=0.0006 |
22.6 16.7 |
0.70 P=0.032 |
15 6 |
36 12 |
|
| Souglakos J, et al. 2006 | III | OS | FOLFOXIRI FOLFIRI |
137 146 |
43 33.6 |
P=0.17 | 8.4 (7.0–10.2)* 6.9 (6.0–7.7)* |
P=0.17 | 21.5 19.5 |
P=0.34 | |||
| Bevacizumab | |||||||||||||
| Loupakis F, et al. 2014 | III | PFS | FOLFOXIRI+bev FOLFIRI+bev |
252 256 |
65.1 53.1 |
1.64 P=0.006 |
12.1 (10.9–13.2) 9.7 (9.3–10.9) |
0.75 P=0.003 |
31.0 (26.9–35.1) 25.8 (22.7–30.8) |
0.79 P=0.054 |
15 12 |
||
| Masi G, et al. 2010 | II | PFS | FOLFOXIRI+bev | 57 | 77 | 13.1 (10.9–15.2) | 30.9 (24.9–35.2) | 26 | 40 | ||||
| Gruenberger T, et al. 2015 | II | Resection rate |
FOLFOXIRI+bev | 41 Liver limited |
81 | 18.6 (12.9–22.3) | NA | 49 | 17.1** | ||||
| Bruera G, et al. 2010 | II | RR | Fir-bev/FOx | 50 | 82 | 12 (range; 3–46) | 28 (range; 3–47) | 22 | |||||
| Stein A, et al. 2015 | II | PFS | FOLFOXIRI+bev | 90 | 64 | 11.1 (9.4–12.0) | 32.2 (22.6–36.9) | 18 | |||||
| Cetuximab | |||||||||||||
| Saridaki Z, et al. 2012 | II | RR | FOLFOXIRI+cet | 30 KRAS wt |
70 | 10.2 (7.1–13.4)* | 30.3 (18.8–41.9) | 37 | 62 | 10.2 | |||
| Garufi C,et al. 2010 | II | Resection rate |
chrono-IFLO+cet | 43 Liver limited |
79.1 | 14 (11–17) | 37 (21–53) | 60 | 11** | ||||
| Assenat E, et al. 2011 | II | Complete RR |
FOLFIRINOX+cet | 24 KRAS wt |
83.3 | 9.9 (6.2–12.5) | NR | ||||||
| Folprecht G, et al. 2014 | I | MTD | FOLFOXIRI+cet | 20 | 75 | 16.0 (12.6–19.4) | 33.0 (26.2–39.8) | ||||||
| Panitumumab | |||||||||||||
| Fornaro L, et al. 2013 | II | RR | FOLFOXIRI+pani | 37 RAS/BRAF wt |
89 | 11.3 (9.7–12.9) | NR | 35 | |||||
*
TTP; time to tumor progression
**
patients underwent R0/R1 resection or all patients resected
Abbreviation: RR, response rate; PFS, progression-free survival; OS, overall survival; MTD, maximum tolerable dosage; LLD, liver-limited disease; NA, not applicable; NR, not reached; FIr-bev/FOx, 5-FU plus alternating irinotecan/bevacizumab or oxaliplatin