Introduction
Methods
Data sources and search strategy
Selection criteria
Data extraction and quality assessment
Statistical analyses
Results
Characteristics of the included studies
Trial | Study arms | Number of randomized patients | Age (Mean, range or SD) | Sex (Male,%) | Line | Outcomes | ||||
---|---|---|---|---|---|---|---|---|---|---|
I | C | I | C | I | C | I | C | |||
Antonio 2021 [26] | modified FOLFOX-6/modified CAPOX + bevacizumab administered 4 days before chemotherapy | modified FOLFOX-6/modified CAPOX + bevacizumab administered on the same day as chemotherapy | 115 | 115 | 61(53–68) | 63(56–68) | 60 | 58.3 | F | GHS (ST and LT) |
ALTER0703 [27] | Anlotinib | Placebo | 282 | 137 | 56.2 ± 10.5 | 55.2 ± 10.8 | 63 | 66 | S | GHS (ST and LT) |
Liu 2020 [28] | Traditional Chinese Medicine Combined With Chemotherapy and Cetuximab or Bevacizumab | Placebo Combined With Chemotherapy and Cetuximab or Bevacizumab | 160 | 160 | 63.89 ± 10.11 | 62.19 ± 7.84 | 54 | 69 | F + S | GHS (LT) |
CONCUR | Regorafenib | placebo | 136 | 68 | 58.0 (31.0–79.0) | 55.0 (33.0–84.0) | 66 | 45 | S | GHS(LT) HUS |
Xu 2017 [31] | Famitinib | placebo | 99 | 55 | 55 (24–70) | 54 (32–71) | 57 | 60 | S | GHS (ST and LT) |
BEACON CRC [21] | I1:Encorafenib + cetuximab with binimetinib;I2:Encorafenib + cetuximab;I3:Irinotecan or FOLFIRI + cetuximab | 224/220/221 | 62 (26–85)/61(30–91)/60(27–91) | 47/52/43 | S | GHS (ST and LT) | ||||
PRODIGE 18 [32] | Bevacizumab + chemotherapy | Cetuximab + chemotherapy | 65 | 67 | 61 (33–83) | 63(37–84) | 63 | 66 | S | GHS (ST and LT) |
NORDIC9 [33] | reduced-dose S1 + oxaliplatin | S1 | 71 | 79 | 77.8 ± 13.7 | 78.4 ± 4.0 | 49 | 51 | F | GHS (ST and LT) |
KEYNOTE-177 [22] | pembrolizumab | mFOLFOX6 or FOLFIRI | 153 | 154 | 63.0(24–93) | 62.5(26–90) | 46 | 53 | F | GHS (ST and LT) HUS |
Valentino [34] | Panitumumab + 5-FU/LV | Panitumumab | 107 | 103 | 64 (54–69) | 63 (56–70) | 66 | 65 | F | GHS(ST and LT) |
Jane 2020 [35] | FOLFOX + SIRT | FOLFOX | NA | NA | NA | NA | NA | NA | F | GHS (ST and LT) |
Filippo 2020 [36] | Capecitabine + temozolomide | FOLFIRI | 43 | 43 | 70.0(63.0–74.5) | 67.0(61.0–73.0) | 42 | 56 | S | GHS (ST and LT) |
REVERCE [37] | Regorafenib | cetuximab | 51 | 50 | 68(62–74) | 65(57–70) | 61 | 66 | S | HUS |
NORDIC-VII [38] | I1:FLOX/I2: Cetuximab + FLOX/C:Cetuximab and intermittent FLOX | 172/171/169 | 60.1(29.9–74.8)/ 59.5(26.9–74.4)/62.2(35.7–74.9) | 55/61/62 | F | GHS (ST and LT) | ||||
CRYSTAL Subgroup 1 [39] | Cetuximab + FOLFIRI | FOLFIRI | 170 | 181 | 60(24–79) | 59(19–82) | 64 | 66 | F | GHS (ST and LT) |
AIO KRK 0207 [40] | I1:fluoropyrimidine(FP) + BEV/I2:BEV/C:No treatment | 136/142/135 | 64(25–82)/65(32–82)/66(32–82) | 67/68/63 | S | GHS (ST and LT) | ||||
CRYSTAL Subgroup 2 [41] | Cetuximab + FOLFIRI | FOLFIRI | 300 | 327 | 60(24–80) | 59(19–84)) | 63 | 62 | F | GHS (ST and LT) |
Yong 2013 [42] | Capecitabine | Capecitabine + oxaliplatin (CAPOX) | 40 | 40 | 71.0 (66–81) | 72.0 (65–79) | 58 | 55 | F | GHS (ST and LT) |
PRIME 1 [43] | Panitumumab + FOLFOX4 | FOLFOX4 | 284 | 292 | 60.5(10.5) | 60.1(11.3) | 67 | 64 | F | HUS |
PRIME 2 [43] | Panitumumab + FOLFIRI | FOLFIRI | 263 | 267 | 60.1(10.1) | 60.6(10.1) | 61 | 64 | S | HUS |
DaVINCI [44] | Irinotecan | FOLFIRI | 44 | 44 | 66(26–84) | 64(35–78) | 59 | 70 | S | GHS (LT) |
Dawn 2010 [45] | Panitumumab + BSC | BSC | 112 | 96 | 62 (10) | 62 (10) | 71 | 65 | S | HUS |
CO.17 Trial [46] | Petuximab + BSC | BSC | 287 | 285 | NA | NA | NA | NA | S | GHS (ST and LT) |
Jolien 2009 [47] | Chemotherapy + bevacizumab | Chemotherapy + bevacizumab + cetuximab | 368 | 368 | 62(27–83) | 62(33–80) | 56 | 63 | F | GHS (LT) |
Southern Italy Cooperative Oncology study 0401 [48] | OXAFAFU | OXXEL | 164 | 158 | 65 (37–79) | 64 (39–84) | 54 | 66 | F | GHS (ST and LT) |
EPIC [49] | Cetuximab + irinotecan | Irinotecan | 648 | 650 | 61(23–85) | 62(21–90) | 63 | 63 | S | GHS (ST and LT) |
Rohit 2004 [50] | 8 cycle irinotecan | Continue Irinotecan | 30 | 25 | 65(42–76) | 64(45–78) | 67 | 64 | S | GHS (ST and LT) |
EORTCG Group Study 40,952 [51] | FU24h/FU24h + LV/FU + LV | 166/164/167 | 61(25–76)/62(23–76)/61(32–76) | 54/62/63 | F | GHS (ST and LT) | ||||
Charles 2003 [52] | Weekly Irinotecan | Every 3-Week Irinotecan | 95 | 196 | NA | NA | 62 | 58 | S | GHS (ST and LT) |
Saltz 2000 [53] | Irinotecan + fluorouracil + leucovorin | Fluorouracil and leucovorin | 231 | 226 | 62(25–85) | 61(19–85) | 65 | 54 | F | GHS (ST and LT) |
Hill 1995 [54] | Fluorouracil + Interferon Alfa-2b | Fluorouracil | 77 | 78 | 57(16–79) | 61(36–78) | 68 | 54 | F | GHS (ST and LT) |
ASPECCT [55] | Panitumumab | Cetuximab | 499 | 500 | 61.0 (54–67) | 60.5 (53–68) | 63 | 64 | S | HUS |
Peeters 2014 [56] | Panitumumab + FOLFIRI | Panitumumab | 303 | 294 | 60 (28–84) | 61 (29–86) | 62 | 65 | S | HUS |
PICCOLO [57] | Panitumumab + irinotecan | irinotecan | 230 | 230 | 64 (57–70) | 63 (56–69) | 70 | 69 | S | GHS (LT) |
LUME-Colon 1 [58] | Nintedanib | Placebo | 386 | 382 | 62 (22–85) | 62 (23–83) | 61 | 57 | S | GHS (LT) |
CORRECT [59] | Regorafenib | placebo | 505 | 255 | 61 (54·0–67·0) | 61 (54·0–68·0) | 62 | 60 | S | GHS (LT) and HUS |
Yong 2012 [60] | S-1 + oxaliplatin | CAPOX | 168 | 172 | 61 (53–66) | 60 (52–66) | 65 | 59 | F | GHS (LT) |
PanaMa [61] | Panitumumab + FU/FA | FU/FA | 125 | 123 | 66 (44–84) | 65 (30–86) | 70 | 63 | F | GHS (ST and LT) |