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.
From randomization date to second disease progression.
From randomization to disease progression or death (not including induction time).
PFS, or, if induction therapy was reintroduced, addition of the initial PFS and the PFS of the reintroduction.