Table 1. Characteristics of relevant studies included in meta-analysis.
| Source | Scope | Treatment | Sample Size | Age, Median (range), y | Outcomes and raw HRs with 95% CI | Additional survival statistics (months) |
|---|---|---|---|---|---|---|
| Maintenance therapy with intermittent chemotherapy | ||||||
| Chibaudel 2009 (OPTIMOX2) | Multicenter, France |
Induction: mFOLFOX7 every 2 weeks *6cycles; Maintenance (sLV5FU2; restart mFOLFOX7 at PD); CFI (observation; restart mFOLFOX7 at PD) |
98 104 |
67 (35–80) 67 (31–80) |
DDC, 0.71 (0.51–0.99, P = 0.046); PFS, 0.61 (P = 0.0017); OS, 0.88 (P = 0.42) |
DDC3: 13.1 vs. 9.2; PFS: 8.6 vs. 6.6; OS: 23.8 vs. 19.5; ORR: 59.2% vs. 59.6% |
| Simkens 2015 (CAIRO3) | Multicenter, Netherlands |
Induction: (BEV+XELOX) every 3 weeks*6 cycles; Maintenance: BEV (7.5 mg/kg) + Cape (625 mg/m2 bid); restart BEV+XELOX at PD); CFI: observation; restart BEV+ XELOX at PD) |
278 279 |
63 (26–81) 64 (31–81) |
PFS1, 0.40 (0.36–0.52, P < 0.0001); PFS2, 0.63 (0.53–0.77, P < 0.0001); OS, 0.83 (0.68–1.01, P = 0.06) |
PFS12: 8.5 (6.5–10.3) vs. 4.1 (3.9–4.2) PFS21: 11.7 (10.1–13.3) vs. 8.5 (7.4–10.4) OS: 25.9 (23.7–28.4) vs. 22.4 (20.8–24.9) |
| Hegewisch 2015 (AIO 0207) (Arm A VS Arm C) | Multicenter, Germany |
Induction: (BEV+FOLFOX) every 2 weeks*12cs/(BEV+XELOX) every 3 weeks*8 cycles; Maintenance (BEV+5FU; restart BEV+FOLFOX/XELOX at PD); CFI (observation; restart BEV+FOLFOX/XELOX at PD) |
158 158 |
64 (25–82) 66 (32–82) |
PFS, 0.48 (0.37–0.61, P < 0.0001); TFS, 0.76 (0.59–0.99, P = 0.038) |
PFS2: 6.3 (2.8–7.6) vs. 3.5 (2.9–4.1) OS: 20.2 (17.7–24.3) vs. 23.1 (19.2–27.3) |
| Hegewisch 2015 (AIO 0207) (Arm B vs. Arm C) | Multicenter, Germany |
Induction: (BEV + FOLFOX) every 2 weeks*12 cycles/(BEV+XELOX) every 3 weeks*8cycles; Maintenance (BEV; restart BEV+FOLFOX/XELOX at PD); CFI (observation; restart BEV + FOLFOX/XELOX at PD) |
156 158 |
65 (32–82) 66 (32–82) |
PFS, 0.69 (0.55–0.87, P = 0.0018) | PFS2: 4.6 (4.0–5.3) vs. 3.5 (2.9–4.1) OS: 21.9 (18.7–26.9) vs. 23.1 (19.2–27.3) |
| Maintenance therapy with continuous chemotherapy | ||||||
| Tournigand 2006 (OPTIMOX1) | Multicenter, France |
Induction: FOLFOX7 every 2 weeks*6cs; Maintenance: (Slv5FU2 every 2 weeks*12cs; FOLFOX7 every 2 weeks*6 cycles); Continuous: (FOLFOX4 every 2 weeks until PD) |
309 311 |
64 (32–80) 65 (29–80) |
DDC, 0.99 (0.81–1.15, P = 0.89); PFS, 1.06 (0.89–1.20, P = 0.47); OS, 0.93 (0.72–1.11, P = 0.49) |
DDC: 10.6 vs. 9.0; PFS: 8.7 vs. 9.0; OS: 21.2 vs. 19.3; ORR: 59.2% vs. 58.5% |
| DÍAZ-RUBIO 2012 (MACRO) | Multicenter, Spain |
Induction: (BEV+ XELOX) every 3 weeks*6 cycles Maintenance: BEV only until PD; Continuous: BEV+XELOX until PD |
241 239 |
64 (33–82) 63 (30–80) |
PFS, 1.10 (0.89–1.35) OS, 1.05 (0.85–1.30) |
PFS: 9.7 (8.3–10.6) vs. 10.4 (9.4–11.9); OS: 20.0 (18.0–23.3) vs. 23.2 (19.8–26.0); ORR: 49% vs. 47% |
| Yalcin 2013 | Multicenter, Turkey |
Induction: (BEV+XELOX) every 3 weeks*6 cycles; Maintenance: BEV+Cape until PD); Continuous: BEV+XELOX until PD |
61 62 |
56 (34–82) 59 (25–77) |
PFS, 1.67 (NR), P = 0.002 OS, NR, P = 0.100 |
PFS: 11.0 (9.1–12.9) vs. 8.3 (7.1–9.5); OS: 23.8 (22.0–28.8) vs. 20.2 (18.4–23.5); ORR: 66.7% vs. 59.0% |
Abbreviations: BEV = Bevacizumab; Cape = capecitabine; Cet = cetuximab; CFI = chemotherapy-free interval; FLOX = 5-FU/leucovorin/oxaliplatin; FOLFOX = folinic acid(leucovorin)/5-FU/oxaliplatin; m = modified; mos = months; NR = not reported; PD = disease progression; 5FU = 5-fluorouracil; PFS = progression-free survival; OS = overall survival; DDC = duration of disease control; RR = objective response rate.
1
From randomization date to second disease progression.
2
From randomization to disease progression or death (not including induction time).
3
PFS, or, if induction therapy was reintroduced, addition of the initial PFS and the PFS of the reintroduction.