Table 4 Comparison of efficacy and safety of different chemotherapy or targeted therapy regimens in patients with biliary tract cancer
From: Chemotherapy and targeted therapy for advanced biliary tract cancers: an umbrella review
First author, Year | Type of Chemotherapy | Study design | Clinical Outcome | Effects model | MA metric | Estimates | 95%CI-low | 95%CI-up | p-value | I2% | P-value for TES | P-value forEgger test | MA Quality Assessment |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ALESSANDRO RIZZO,2020 [22] | G-based + anti-EGFR vs. G-based | RCTs | OS | Random | HR | 0.82 | 0.64 | 1.06 | 0.13 | 33 | 0.2472 | NA | Cochrane ROB Tool |
PFS | Fixed | HR | 0.88 | 0.73 | 1.08 | 0.22 | 0 | 1 | NA | ||||
ORR | Fixed | RR | 1.34 | 0.91 | 1.99 | 0.14 | 0 | 1 | NA | ||||
Toxicities–Neutropenia | Fixed | RR | 1.95 | 1.13 | 3.36 | 0.02 | 0 | 0.2367 | NA | ||||
Toxicities–Thrombocytopenia | Fixed | RR | 1.69 | 0.99 | 2.87 | 0.05 | 0 | 1 | NA | ||||
Toxicities–Skin rash | Fixed | RR | 18.11 | 5.13 | 63.91 | < 0.00001 | 0 | 0.8343 | NA | ||||
Toxicities–Diarrhea | Fixed | RR | 1.65 | 0.89 | 3.04 | 0.11 | 0 | 1 | NA | ||||
Toxicities–Fatigue | Fixed | RR | 2.01 | 0.91 | 4.44 | 0.09 | 0 | 1 | NA | ||||
Lawrence Chen,2016 [16] | GP vs. G | RCTs | Duration of OS | Random | WMD | -3.52 | -5.14 | -1.35 | 0.0008 | 0 | — | NA | Cochrane ROB Tool |
OS | Random | HR | 0.65 | 0.53 | 0.79 | < 0.00001 | 0 | 0.8264 | NA | ||||
Duration of PFS | Random | WMD | -2.60 | -3.81 | -1.40 | < 0.00001 | 0 | — | NA | ||||
PFS | Random | HR | 0.63 | 0.52 | 0.76 | < 0.00001 | 0 | 0.8544 | NA | ||||
ORR | Random | OR | 0.53 | 0.31 | 0.88 | 0.02 | 0 | 0.6220 | NA | ||||
GP + anti-EGFR vs. GP | Duration of OS | Random | WMD | -1.49 | -2.56 | -0.43 | 0.006 | 0 | — | NA | |||
OS | Random | HR | 0.90 | 0.70 | 1.15 | 0.39 | 0 | 1 | NA | ||||
Duration of PFS | Random | WMD | -0.07 | -1.91 | 1.77 | 0.94 | 0 | — | NA | ||||
PFS | Random | HR | 0.79 | 0.63 | 0.99 | 0.04 | 0 | 1 | NA | ||||
ORR | Random | OR | 0.56 | 0.38 | 0.83 | 0.003 | 0 | 0.9783 | NA | ||||
Ting Zheng,2020 [19] | GP vs. FP | Restrospective;RCTs | ORR | Fixed | RR | 1.13 | 0.80 | 1.58 | > 0.05 | 44.9 | 0.482 | 0.187 | Cochrane ROB Tool; NOS |
DCR | Fixed | RR | 1.02 | 0.91 | 1.13 | > 0.05 | 12 | 0.7508 | 0.209 | ||||
PFS/TTP | Fixed | HR | 0.95 | 0.86 | 1.05 | > 0.05 | 0 | 1 | NA | ||||
OS | Fixed | HR | 1.06 | 0.98 | 1.14 | > 0.05 | 37.3 | 0.2265 | NA | ||||
Toxicities–Neutropenia | NA | NA | 16.7 (9.3–25.8) vs. 19.3 (3.7–43.3) | < 0.001 | 91.4 | — | NA | ||||||
Toxicities–Anemia | NA | NA | 5.6 (1.1–13.3) vs. 13.1 (7.8–19.5) | < 0.001 | 81.5 | — | NA | ||||||
Toxicities–Trombocytopenia | NA | NA | 6 (2.7–10.5) vs. 10.3 (2.7–22.1) | < 0.001 | 79.5 | — | NA | ||||||
Toxicities–Nausea/Vomiting | NA | NA | 5.7 (4–7.7) vs. 7.8 (5.6–10.3) | < 0.001 | 0 | — | NA | ||||||
Toxicities–Anorexia | NA | NA | 2.2 (1–3.7) vs. 3.1 (0.2–9.3) | < 0.001 | 64.9 | — | NA | ||||||
Toxicities–Nephropathy | NA | NA | 1.1 (0.2–2.7) vs. 2.9 (0.7–6.6) | < 0.001 | 67.6 | — | NA | ||||||
Toxicities–Neuropathy | NA | NA | 0.9 (0.3–1.8) vs. 2.6 (1.4–4.1) | < 0.001 | 47.9 | — | NA | ||||||
Xin ZHUANG,2017 [21] | G-based + anti-EGFR vs. G-based | RCTs | Toxicities–Neutropenia | Fixed | OR | 1.37 | 0.89 | 2.12 | 0.15 | 0 | 0.3165 | NA | Jadad Scale |
Toxicities–Thrombocytopenia | Fixed | OR | 1.4 | 0.83 | 2.39 | 0.21 | 48 | 1 | NA | ||||
Toxicities–Anemia | Fixed | OR | 1.21 | 0.62 | 2.38 | 0.57 | 0 | 1 | NA | ||||
Toxicities–Peripheral neuropathy | Fixed | OR | 1.52 | 0.81 | 2.88 | 0.19 | 0 | 0.2096 | NA | ||||
Toxicities–Increased AST/ALT | Fixed | OR | 1.4 | 0.82 | 2.39 | 0.22 | 0 | 1 | NA | ||||
Heng Liu,2014 [18] | G-based vs. non-G-based | RCTs | DRR | Fixed | OR | 1.39 | 0.81 | 2.40 | 0.24 | 48 | 0.8733 | 1.00 | Jadad Scale |
DCR | Random | OR | 1.48 | 0.43 | 5.07 | 0.53 | 81 | 0.8312 | 0.23 | ||||
PFS(months) | Random | OR | 1.78 | -0.39 | 3.96 | 0.11 | 99 | — | 0.55 | ||||
OS(months) | Random | OR | 1.51 | -1.37 | 4.38 | 0.3 | 99 | — | 1.00 | ||||
Toxicities–Leukopenia | Random | OR | 7.17 | 1.43 | 36.08 | 0.02 | 64 | 0.8917 | NA | ||||
Toxicities–Anemia | Fixed | OR | 7.04 | 2.59 | 19.12 | 0.00001 | 0 | 0.1356 | NA | ||||
Toxicities–Neutropenia | Random | OR | 4.63 | 0.95 | 22.50 | 0.06 | 82 | 0.9924 | NA | ||||
Toxicities–Thrombocytopenia | Random | OR | 2.79 | 0.66 | 11.81 | 0.16 | 70 | 0.3348 | NA | ||||
Toxicities– Increased ALT level | Fixed | OR | 1.11 | 0.56 | 2.23 | 0.76 | 46 | 1 | NA | ||||
G-based vs. G | Toxicities–Leukopenia | Random | OR | 1.82 | 1.13 | 2.94 | 0.01 | 0 | 1 | NA | |||
Toxicities–Anemia | Fixed | OR | 1.96 | 1.07 | 3.62 | 0.03 | 54 | 0.3617 | NA | ||||
Toxicities–Neutropenia | Random | OR | 1.78 | 1.19 | 2.66 | 0.005 | 0 | 0.6637 | NA | ||||
Toxicities–Thrombocytopenia | Random | OR | 1.13 | 0.6 | 2.14 | 0.71 | 0 | 1 | NA | ||||
Toxicities– Increased ALT level | Fixed | OR | 0.76 | 0.47 | 1.25 | 0.29 | 66 | 1 | NA | ||||
Sheng Zhao,2016 [17] | G-based + anti-VEGFR/EGFR vs. G-based | RCTs | Toxicities– Nausea | NA | RR | 1.01 | 0.41 | 2.47 | 0.98 | No significant | — | NA | Jadad Scale |
Toxicities– Vomiting | NA | RR | 0.71 | 0.31 | 1.60 | 0.41 | No significant | — | NA | ||||
Toxicities– Diarrhea | NA | RR | 2.48 | 1.2 | 5.10 | 0.014 | No significant | — | NA | ||||
Alessandro Rizzo,2022 [26] | Fluoropyrimidine-based doublet CHT vs. ASC or 5-FU/LV | RCTs | OS | Fixed | HR | 0.63 | 0.49 | 0.80 | < 0.0001 | 0 | 0.5867 | NA | Cochrane ROB Tool |
DCR | Fixed | OR | 5.18 | 3.3 | 10.23 | NA | 84 | 0.9772 | NA | ||||
ORR | Random | OR | 3.24 | 1.18 | 8.92 | NA | 0 | 1 | NA | ||||
Wen-Jie Ma,2020 [27] | Fluoropyrimidine-based vs. Observation | RCTs | OS | Random | HR | 0.83 | 0.7 | 0.99 | 0.04 | 13 | 0.5350 | 0.62 | Jadad Scale |
G-based vs. Observation | OS | Random | HR | 0.91 | 0.74 | 1.12 | 0.37 | 2 | 1 | 0.62 | |||
Julien Edeline,2022 [28] | G-based vs. Observation | RCTs | RFS-All Patients | NA | HR | 0.91 | 0.71 | 1.16 | 0.46 | NA | — | NA | NA |
RFS-R1 resection Patients | NA | HR | 1.10 | 0.58 | 2.07 | 0.77 | NA | — | NA | ||||
RFS-N + tumor Patients | NA | HR | 0.86 | 0.60 | 1.23 | 0.40 | NA | — | NA | ||||
OS-All Patients | NA | HR | 1.03 | 0.78 | 1.35 | 0.85 | NA | — | NA | ||||
OS-R1 resection Patients | NA | HR | 1.25 | 0.63 | 2.49 | 0.52 | NA | — | NA | ||||
OS-N + tumor Patients | NA | HR | 0.99 | 0.67 | 1.46 | 0.94 | NA | — | NA | ||||
Abdel-Rahman O,2018 [29] | G + S-1 vs. S-1 | RCTs | All-cause mortality at 1 year | Random | RR | 0.61 | 0.33 | 1.13 | 0.12 | 76 | 0.2928 | NA | Cochrane ROB Tool |
ORR(S-1 vs.G + S-1) | Random | RR | 2.46 | 1.27 | 4.57 | 0.0073 | 0 | 0.5223 | NA | ||||
Toxicities–Grade 1—4 Anaemia | Random | RR | 1.26 | 1.00 | 1.59 | 0.052 | 0 | 1 | NA | ||||
Toxicities–Grade 1—4 Thrombocytopenia | Random | RR | 2.45 | 1.39 | 4.32 | 0.0019 | 0 | 0.6803 | NA | ||||
Toxicities–Grade 1—4 Neutropenia | Random | RR | 3.30 | 1.04 | 10.50 | 0.043 | 66 | 0.4714 | NA | ||||
Toxicities–Febrile Neutropenia | Random | RR | 2.97 | 0.32 | 27.87 | 0.34 | 0 | 1 | NA | ||||
Yan Li,2019 [30] | Observation vs. FOLFOX-4 | Restrospective;RCTs | OS | NA | HR | 3.40 | 1.70 | 6.70 | NA | NA | — | NA | NA |
XP vs. GP | OS | NA | HR | 0.74 | 0.51 | 1.10 | NA | NA | — | NA | |||
G + S-1 vs. GC | OS | NA | HR | 1.10 | 0.71 | 1.50 | NA | NA | — | NA | |||
Jie Ying,2019 [31] | G-based CHT vs. single CHT(mainly FU alone) | Restrospective;RCTs | DCR | NA | RR | 1.36 | 1.04 | 1.80 | 0.012 | NA | — | Funnel plot only | NOS |
Fluoropyrimidine-based CHT vs. single TAs | DCR | NA | RR | 0.78 | 0.61 | 1.00 | 0.03 | NA | — | Funnel plot only | |||
Taxanes-based CHT vs. single CHT(mainly FU alone) | DCR | NA | RR | 1.54 | 1.02 | 2.32 | 0.02 | NA | — | Funnel plot only | |||
Fluoropyrimidine-based CHT vs. single CHT(mainly FU alone) | 1-year OS | NA | RR | 0.51 | 0.29 | 0.87 | 0.006 | NA | — | Funnel plot only | |||
Wei Zheng,2019 [32] | G + S-1 vs. G | RCTs | ORR | NA | OR | 4.72 | 1.31 | 17.02 | NA | NA | — | Funnel plot only | NA |
OS | NA | HR | 0.43 | 0.20 | 0.93 | NA | NA | — | Funnel plot only | ||||
G + S-1 vs. 5-FU | ORR | NA | OR | 9.08 | 1.56 | 89.20 | NA | NA | — | Funnel plot only | |||
OS | NA | HR | 0.51 | 0.28 | 0.96 | NA | NA | — | Funnel plot only | ||||
CapC vs.5-FU | ORR | NA | OR | 5.46 | 1.07 | 56.63 | NA | NA | — | Funnel plot only | |||
GEMOX vs. 5-FU | OS | NA | HR | 0.57 | 0.32 | 0.96 | NA | NA | — | Funnel plot only | |||
FP vs. 5-FU | OS | NA | HR | 1.88 | 1.07 | 3.16 | NA | NA | — | Funnel plot only | |||
Yanfeng Jiang,2021 [33] | Observation vs. Folfox-4 | Restrospective;RCTs | PFS | NA | HR | 2.88 | 1.05 | 7.93 | NA | NA | — | Funnel plot only | Cochrane ROB Tool |
Observation vs. C-GEMOX | PFS | NA | HR | 2.82 | 1.20 | 6.62 | NA | NA | — | Funnel plot only | |||
Observation vs. GEMOX + erlotinib | PFS | NA | HR | 3.21 | 1.38 | 7.56 | NA | NA | — | Funnel plot only | |||
GP + cediranib vs. 5-FU | ORR (5-FU vs.GP + cediranib) | NA | OR | 0.13 | 0.02 | 0.87 | NA | NA | — | Funnel plot only | |||
Toxicities–Neutropenia | NA | OR | 0.04 | 0 | 0.65 | NA | NA | — | Funnel plot only | ||||
GP vs. 5-FU | Toxicities–Neutropenia | NA | OR | 0.06 | 0.01 | 0.50 | NA | NA | — | Funnel plot only | |||
G + S-1 vs. 5-FU | Toxicities–Neutropenia | NA | OR | 0.05 | 0 | 0.55 | NA | NA | — | Funnel plot only | |||
C-GEMOX vs. 5-FU | Toxicities–Neutropenia | NA | OR | 0.08 | 0.01 | 0.60 | NA | NA | — | Funnel plot only | |||
RAM + GP vs. 5-FU | Toxicities–Neutropenia | NA | OR | 0.03 | 0 | 0.38 | NA | NA | — | Funnel plot only | |||
MER + GP vs. 5-FU | Toxicities–Neutropenia | NA | OR | 0.03 | 0 | 0.41 | NA | NA | — | Funnel plot only | |||
XELOX vs. G + XELOX | Toxicities–Vomiting | NA | OR | 0.07 | 0 | 0.98 | NA | NA | — | Funnel plot only | |||
XELOX vs. GEMOX + erlotinib | Toxicities– Diarrhea | NA | OR | 0.09 | 0.01 | 0.63 | NA | NA | — | Funnel plot only | |||