Table 1 The principal characteristics of eligible articles
First author | Year | Clinicaltrials.gov | Study phase | MSI/MMR status | No. patients treated with ICIs | Treatment line | ICIs agent | Dose | Combination drug |
Gou M [15] | 2022 | NA | Retrospective, SA | non-MSI-H/pMMR | 45 |  ≥ 3 | anti-PD-1 | Pembro, Sin, Camre: 200 mg; Nivo: 3 mg/kg, q3w | Fruquintinib |
Antoniotti C [13] | 2022 | NCT03721653 | RCT, phase II | pMMR | 132 | 1 | Atezo | 840 mg, q2w | FOLFOXIRI + Bevacizumab |
Xu YJ [16] | 2022 | NA | Retrospective, SA | MSS/pMMR | 30 |  ≥ 3 | anti-PD-1 | Tori: 240 mg q3w, Camre: 200 mg q2 or 3w, Nivo: 240 mg q2w, Pembro, Sin, tislelizumabor: 200 mg q3w | Rego |
Morano F [14] | 2022 | NCT03832621 | MC, SA, phase II | MSS | 33 |  ≥ 2 | IPI and Nivo | IPI: 1 mg/kg q8w, Nivo: 480 mg q4w | Temozolomide |
Mettu NB [17] | 2022 | NCT02873195 | RCT, phase II | MSS/pMMR | 69 |  ≥ 2 | Atezo | 840 mg, q2w | Capecitabine + Bevacizumab |
Rahma OE [11] | 2022 | NCT02298959 | MC, phase IB | MSS | 6 |  ≥ 2 | Pembro | 2 mg/kg, q2w | Ziv-aflibercept |
Kim RD [18] | 2022 | NCT03712943 | OL, SA, phase I/Ib | pMMR | 51 |  ≥ 3 | Nivo | 240 mg | Rego |
Redman JM [19] | 2022 | NCT03050814 | RCT, phase II | MSS | 16 | 1 | Ave | 10 mg/kg q2w | AdCEA Vaccine + mFOLFOX6 + Bevacizumab |
Fukuoka S [20] | 2020 | NCT03406871 | OL, phase Ib | MSS/pMMR | 25 |  ≥ 3 | Nivo | 3 mg/kg, q2w | Rego |
Eng C [10] | 2019 | NCT02788279 | RCT, MC, OL, phase III | MSS/MSI-L | 170 | NA | Atezo | 840Â mg, q2w | Cobimetinib |
83 | NA | Atezo | 1200Â mg, q3w | None | |||||
Kawazoe A [21] | 2020 | NCT02851004 | MC, phase I/II | MSS | 40 | NA | Pembro | 200Â mg, q3w | Napabucasin |
Ren C [22] | 2020 | NCT03912857 | Prospective, SA, OL, phase II | MSS | 10 | NA | Camre | 200Â mg, q2w | Apatinib |
Kawazoe A [23] | 2021 | UMIN000032801 | OL, phase Ib | MSS | 25 |  ≥ 2 | Nivo | 3 mg/kg, q2w | TAS-116 (Pimitespib) |
Parikh AR [12] | 2021 | NCT03104439 | SA, non-randomized, phase II | MSS | 27 |  ≥ 2 | IPI and Nivo | Nivo: 240 mg and IPI: 1 mg/kg | Radiation |
13 |  ≥ 2 | None | |||||||
Wang C [24] | 2020 | NA | Retrospective | MSS | 18 |  ≥ 3 | anti-PD-1 | Pembro: 200 mg q3w, Nivo: 240 mg q2w | Rego |
Cousin S [25] | 2021 | NCT03475953 | SA, OL, Phase II | MSS | 47 |  ≥ 2 | Ave | 10 mg/kg q2w | Rego |
Wang C [26] | 2020 | NCT03005002 | SA, Phase II | MSS | 9 |  ≥ 3 | Treme + Durva | Treme: 75 mg q4w + Durva: 1500 mg q4w | Yttrium-90 Liver Radioembolization |
Li J [27] | 2020 | NA | Retrospective | MSS/pMMR | 23 |  ≥ 3 | anti-PD-1 | Nivo, Pembro, Camre, Sin, Tori | Rego |
Hellmann MD [28] | 2019 | NCT01988896 | MC, OL, phase I/Ib | MSS/MSI-L | 62 |  ≥ 1 | Atezo | 800 mg, q2w | Cobimetinib |
Kim DW [29] | 2021 | NCT03332498 | Phase II | pMMR | 31 |  ≥ 2 | Pembro | 200 mg q3w | Ibrutinib |
Patel MR [30] | 2021 | NCT02860546 | SA, phase II | MSS | 18 |  ≥ 3 | Nivo | 3 mg/kg, q2w | Trifluridine/tipiracil |
Bordonaro R [31] | 2021 | NCT02848443 | OL, MC, phase I | MSS | 17 |  ≥ 2 | Nivo | 3 mg/kg, q2w | Trifluridine/tipiracil (FTD/TPI) + oxaliplatin |
Zhou H [32] | 2021 | NA | Retrospective | MSS/pMMR | 21 | 1 | Camre | 200 mg q3w | XELOX + Bevacizumab or Rego |
Yu W [33] | 2021 | NA | Retrospective | MSS | 33 |  ≥ 3 | Tori | 240 mg q3w | Rego |
Sun L [34] | 2021 | NA | Retrospective | MSS | 23 |  ≥ 4 | anti-PD-1 | Tori: 240 mg q3w, Nivo: 200 mg q2w, Sin or Camre: 200 mg q3w | Rego |
28 |  ≥ 4 | Fruquintinib | |||||||
Jiang FE [35] | 2021 | NA | Retrospective | MSS/pMMR | 16 |  ≥ 3 | Camre | 200 mg q3w | Rego or Fruquintinib |
O'Neil BH [36] | 2017 | NCT02054806 | MC, phase Ib | MSS | 19 |  ≥ 1 | Pembro | 10 mg/kg q2w | None |
Yarchoan M [37] | 2020 | NCT02981524 | SA, phase II | pMMR | 17 |  ≥ 3 | Pembro | NA | GVAX colon vaccine |
Taylor K [38] | 2020 | NCT02811497 | MC, OL, phase II | MSS | 15 |  ≥ 4 | Durva | 1500 mg q3w | CC-486 |
Martinelli E [39] | 2021 | NCT04561336 | SA, phase II | MSS | 71 |  ≥ 3 | Ave | 10 mg/kg q2w | Cetuximab |
Wang C [40] | 2021 | NA | Retrospective | MSS | 95 |  ≥ 3 | anti-PD-1/PD-L1 | NA | None |
Lee JJ [41] | 2017 | NCT02260440 | SA, phase II | MSS | 30 |  ≥ 3 | Pembro | 200 mg q3w | Aza |
Fang X [42] | 2022 | NCT05171660 | OL, SA, phase II | MSS | 25 | 1 | Sin | 200Â mg q3w | CapeOx and Bevacizumab |
Bocobo AG [43] | 2021 | NCT03396926 | OL, SA, phase II | MSS | 29 |  ≥ 2 | Pembro | 200 mg q3w | Capecitabine and Bevacizumab |
Huyghe N [44] | 2022 | NCT03608046 | Phase I | MSS | 10 |  ≥ 3 | Ave | 10 mg/kg q2w | Cetuximab and Irinotecan |
13 |  ≥ 3 | ||||||||
First author | Male | median age (range) | Median follow-up time (95%CI) | No. of control | Control | Endpoints | median PFS (95% CI), (month) | median OS (95% CI), (month) | |
Gou M [15] | 30 | 54 (29–85) | NA | 0 | None | ORR, DCR | 3.8 (2.8–4.8) | 14.9 (7.6–21.7) | |
Antoniotti C [13] | NA | (18–75) | 19.9 (IQR, 17.3–23.9) | 67 | FOLFOXIRI + Bevacizumab | PFS | 12·9 (80% CI: 11·9–13·3) | NA | |
Xu YJ [16] | 14 | 57.5 (27–73) | 12 | 0 | None | ORR, DCR | 3.4 (2.2–4.6) | NA | |
Morano F [14] | 17 | 58 (IQR, 53–65) | 23.1 (IQR, 14.9–24.6) | 0 | None | ORR, DCR | 7 | 18.4 | |
Mettu NB [17] | NA | NA | 20.9 | 41 | Capecitabine + Bevacizumab | ORR, PFS | 4.4 (4.1–6.4) | NA | |
Rahma OE [11] | NA | 64 (36–79) | 8.2 | 0 | None | ORR, DCR | 2.5 (0.6–3.3) | 3.3 (0.6–3.4) | |
Kim RD [18] | NA | NA | NA | 0 | None | ORR, DCR | 4.3 (2.3–7.9) | 11.1 (9.7-NR) | |
Redman JM [19] | 11 | NA | NA | 10 | mFOLFOX6 + Bevacizumab | ORR, PFS, OS | 10.1 (3.6–16.1) | 15.1 (5.4–NR) | |
Fukuoka S [20] | 18 | 55 (31–77) | NA | 0 | None | ORR | 7.9 (2.9-NR) | NR (9.8-NR) | |
Eng C [10] | NA | NA | 7.3 (IQR, 3.7–13.6) | 80 | Rego | ORR, PFS, OS | NA | NA | |
NA | NA | 80 | Rego | ORR, PFS, OS | NA | NA | |||
Kawazoe A [21] | 17 | 63 (25–79) | 6.3 (1.1–15.4) | 0 | None | ORR, DCR | 1.6 (1.4–2.1) | 7.3 (5.3–11.8) | |
Ren C [22] | 3 | 54 (40–66) | NA | 0 | None | ORR, DCR | 1.83 (1.80–1.86) | 7.8 (0–17.07) | |
Kawazoe A [23] | 12 | 61 (32–77) | NA | 0 | None | ORR | 3.2 (2.8–4.4) | 13.5 (8.2–15.1) | |
Parikh AR [12] | 22 | 59 (26–83) | NA | 0 | None | ORR, DCR | 2.5 (2.3–2.8) | 10.9 (6.7–15.0) | |
NA | 0 | None | ORR, DCR | NA | NA | ||||
Wang C [24] | 16 | 60 (43–79) | NA | 1 | None | ORR, DCR | 2 | NR | |
Cousin S [25] | 35 | 62 (26–83) | NA | 0 | None | ORR, DCR | 3.6 (1.8–5.4) | 10.8 (5.9–NR) | |
Wang C [26] | 5 | 54 | NA | 0 | None | ORR, DCR | NA | NA | |
Li J [27] | 16 | 50 (33–73) | 7.9 (6.5–9.3) | 0 | None | ORR, DCR | 3.1 (2.32–3.89) | NA | |
Hellmann MD [28] | NA | NA | 4.2 (0.7–40.2) | 0 | None | ORR | NA | NA | |
Kim DW [29] | 16 | 59 (24–73) | NA | 0 | None | ORR, DCR | 1.4 (1.4–1.5) | 6.6 (4.3–12.2) | |
Patel MR [30] | 9 | 56.5 (40–70) | NA | 0 | None | ORR, DCR | 2.2 (1.8–6.0) | 2.8 (1.8–5.1) | |
Bordonaro R [31] | 5 | 64 (33–76) | NA | 0 | None | ORR, DCR | 6 (2–8) | NR (6.5-NR) | |
Zhou H [32] | 11 | 62 (43–78) | 11.5 (10.3–12.7) | 0 | None | ORR, DCR | NA | NA | |
Yu W [33] | 15 | 53.6 (mean) | NA | 0 | None | ORR, DCR | 3.8 | NA | |
Sun L [34] | 13 | 54.6 (mean) | 6.2 (3.9–8.43) | 0 | None | ORR, DCR | NA | NA | |
14 | 53.0 (mean) | 0 | None | ORR, DCR | NA | NA | |||
Jiang FE [35] | 11 | 54 (31–72) | NA | 0 | None | ORR, DCR | NA | NA | |
O'Neil BH [36] | NA | NA | NA | 0 | None | ORR, DCR | NA | NA | |
Yarchoan M [37] | 6 | 58 (44–85) | NA | 0 | None | ORR, DCR | 2.7 (1.6–3.2) | 7.1 (6.0–14.7) | |
Taylor K [38] | 9 | 56 (36–78) | 4.7 | 0 | None | ORR, DCR | NA | NA | |
Martinelli E [39] | NA | NA | 19.5 (12.8–22.8) | 0 | None | ORR, DCR | 3.6 (3.3–3.9) | 11.6 (8.3–15.0) | |
Wang C [40] | 54 | 55 (IQR, 49–64) | NA | 0 | None | ORR, DCR | NA | NA | |
Lee JJ [41] | 17 | 61 (30–79) | NA | 0 | None | ORR, DCR | 2.1 (1.8–2.8) | 6.2 (3.5–8.7) | |
Fang X [42] | 18 | 60 (45–75) | NA | 0 | None | ORR, DCR | NA | NA | |
Bocobo AG [43] | 14 | 55 (36–77) | NA | 0 | None | ORR, DCR | NA | NA | |
Huyghe N [44] | NA | NA | NA | 0 | None | ORR, DCR | NA | NA | |
NA | 0 | None | ORR, DCR | NA | NA | ||||