Background
Methods
Identification and eligibility of relevant studies
Inclusion and exclusion criteria
Inclusion criteria
Exclusion criteria
Definitions and standardization
Data extraction
Statistical analysis
Results
Identification of eligible studies
Study characteristics
Authors (year) [Ref] | Study Design | Region | Patients | CPS | BCLC | ECOG | Aetiology | Treatment | No. of TACE | Duration Time of sorafenib |
---|---|---|---|---|---|---|---|---|---|---|
Erhardt et al. (2014) [33] | Phase II | Germany | 38 | ≤8scores | NA | 0–2 | NA | Continuous sorafenib, interrupted only around TACE | 2.0(mean) | NA |
Dufour et al. (2010) [34] | Phase I Open-label | Switzerland | 14 | A = 93% B = 7% | B = 64% C = 36% | 0 = 93% 1 = 7% | HCV = 29% | Sorafenib started 1 week prior to TACE without pause for TACE | 2.0(median) | NA |
Cabrera et al. (2011) a [35] | Phase II Prospective | USA | 47 | A = 72% B = 28% | B = 81% C = 19% | 0 = 75% 1 = 25% | HCV = 60% | Continuous sorafenib started 2–4 weeks before DEB-TACE | 3.0(median) | NA |
Lee et al. (2011) [36] | Phase II Prospective | South Korea | 59 | A = 93% B = 7% | B = 100% | NA | HBV = 88% | Sorafenib, TACE was performed at every 6–8 weeks | NA | NA |
Pawlik et al. (2011) a [37] | Phase II Prospective | USA | 35 | A = 89% B = 11% | B = 34% C = 66% | 0 = 46% 1 = 54% | HCV = 37% | Continuous sorafenib started 1 week before DEB-TACE | 2.0(median) | NA |
Park et al. (2012) [38] | Phase II Prospective | South Korea | 50 | A = 94% B = 6% | B = 82% C = 18% | 0 = 44% 1 = 56% | HBV = 68% HCV = 18% | Sorafenib started 3 days after TACE | 1.0(median) | 6 month |
Sieghart et al. (2012) [39] | Phase I | Austria | 15 | A = 80% B = 20% | B = 70% C = 30% | 0 = 92% 1 = 8% | HBV = 4% HCV = 20% | Sorafenib started 2 weeks before the first TACE | 3.0(median) | 5.2 month (median) |
Chung et al. (2013) [40] | Phase II Prospective | China and South Korea | 151 | A = 92% B = 8% | A = 16% B = 82% C = 1.9% | 0 = 82% 1 = 18% | NA | Sorafenib started 4–7 days after TACE | 2.1(mean) | NA |
Zhao et al. (2013) [41] | Prospective | China | 222 | A = 86% B = 14% | B = 20% C = 80% | 0 = 44% 1 = 50% 2 = 6% | HBV = 80% HCV = 5% | Continuous sorafenib with no breaks before or after TACE | 2.0(median) | NA |
Pan et al. (2014) [7] | Retrospective | China | 41 | A = 85.4% B = 14.6% | NA | 0 = 48.8% 1 = 51.2% | HBV = 97.6% HCV = 2.4% | Sorafenib was taken 3 days after the first TACE procedure | 2.0(median) | NA |
Chao et al. (2014) [2] | Phase II Prospective | Taiwan | 192 | A = 91.8% B = 7.1% | A = 16.9% B = 81.5% C = 1.6% | 0 = 81.8% 1 = 17.7% 3 = 0.5% | NA | Sorafenib on day 4 (to day 7) after the first TACE (day 1) the interrupt on day 4 before the next TACE | 3.0(median) | NA |
Yao et al. (2015) [32] | Retrospective | China | 50 | A = 88% B = 12% | B = 52% C = 48% | 0 = 46% 1 = 54% | HBV = 84% HCV = 4% | Sorafenib before and after 1 week of TACE | 3.0(median) | 1.4 month (median) |
Cosgrove et al. (2015) a [42] | Phase II | USA | 50 | A = 92% B = 8% | A = 6% B = 32% C = 62% | 0 = 52% 1 = 48% | HBV = 8% HCV = 44% | Sorafenib was started 1 week before the first round of DEB-TACE | 2.0(median) | 1.5 month |
Authors (year) [Ref] | Study Design | Region | Patients | CPS | BCLC | ECOG | Aetiology | Treatment | Quality Assessment |
---|---|---|---|---|---|---|---|---|---|
Martin et al. (2010) a [43] | Prospective | several countries | 150 | ST:B = 31% DT:B = 39% | NA | NA | NA | ST, n = 30; DT, n = 120. | 17 |
Kudo et al. (2011) [15] | Phase III Randomized | Japan | 229 | A = 100% | NA | 0 = 87% 1 = 13% | HBV = 20% HCV = 60% | Sorafenib was given 1–3 months after TACE till progression | 18 |
South Korea | |||||||||
Sansonno et al. (2012) [44] | Phase II prospective randomized | Italy | 40 | A = 100% | B = 100% | 0 = 86% 1 = 24% | HCV = 100% | Sorafenib started 1 month after TACE till progression nor unacceptable toxicity | 4 |
Lencioni et al. (2012) a [10] | Phase II prospective randomized | several countries | 307 | A = 100% | B = 100% | 0 = 100% | NA | Continuous sorafenib 3–7d before TACE | 4 |
Qu et al. (2012) [45] | Retrospective | China | 45 | A = 65% B = 35% | B = 35% C = 65% | 0 = 95% 1 = 5% | HBV = 100% | Sorafenib started after TACE | 17 |
Bai et al. (2013) [46] | Prospective | China | 82 | A = 77% B = 23% | B = 23% C = 77% | 0 = 36.5% 1 = 46.5% | HBV = 87.9% HCV = 4.9% | Continuous sorafenib started within 14d after TACE | 19 |
2 = 14.6% | |||||||||
3 = 1.2% | |||||||||
4 = 1.2% | |||||||||
Muhammad et al. (2013) a [47] | Retrospective | USA | 43 | ST:A = 85% DT:A = 77% | A = 46% B = 15% C = 38% | NA | ST:HCV = 69% DT:HCV = 93% | Sorafenib started with 200 mg bid and then increased to 400 mg in the majority of patients | 20 |
Huang et al. (2013) [48] | Prospective | China | 155 | NA | NA | NA | NA | Sorafenib started within 2 weeks of the first cycle of TACE | 14 |
Hu et al. (2014) [14] | Retrospective | China | 280 | ST:A = 70.7% T:A = 67.7% | B = 100% | NA | ST:HBV = 82.9% T:HBV = 79.8% | Sorafenib after TACE | 20 |
Ohki et al. (2015) [6] | Retrospective | Japan | 95 | ST:A = 70.8% T:A = 56.3% | NA | NA | ST:HCV = 75.0% T:HCV = 67.6% | Sorafenib was started within 2 weeks after TACE | 17 |
Yao et al. (2016) [12] | Prospective | China | 150 | A = 84% B = 16% | B = 42% C = 58% | 0 = 42% 1 = 58% | ST:HBV = 84% T:HBV = 83% | Sorafenib therapy was initiated within 1 week before or after the initial TACE treatment | 20 |
Zhang et al. (2016) [49] | Retrospective | China | 20 | A = 100% | NA | 0 = 85% 1 = 15% | HBV = 80% | Sorafenib was given with an interval of 4-7 days before or after TACE session | 19 |
Wan et al. (2016) [50] | Retrospective | China | 450 | A = 87% B = 13% | NA | 0–1 = 91% 2 = 9% | NA | Oral sorafenib was administrated before or after TACE | 14 |
Varghese et al. (2017) [13] | Retrospective | India | 124 | B:A = 55.9% B = 44.1% C:A = 46.2% B = 53.8% | B = 47.6% C = 52.4% | NA | B:HBV = 37.3% HCV = 18.7% C:HBV = 26.2% HCV = 23% | Sorafenib was introduced 5d after TACE | 17 |
Tumour response, DCR, TTP, OS
Non-comparative studies
Comparative studies
Authors (year) | Combination group (95% CI)/months | TACE alone group (95% CI)/months | HR (95% CI) |
---|---|---|---|
Kudo et al. (2011) [15] | 5.4(3.8–7.2) | 3.7 (3.5–4.0) | 0.87(0.70–1.09) |
Sansonno et al.(2012) [44] | 9.2 | 4.9 | 2.5(1.66–7.56) |
Lencioni et al. (2012) [10] | 5.6 | 5.5 | 0.797 (0.588–1.08) |
Bai et al. (2013) [46] | 6.3 | 4.3 | 0.6 (0.422–0.853) |
Muhammad et al. (2013) [47] | NA | NA | 0.93 (0.45–1.89) |
Huang et al. (2013) [48] | 5.4 | 3.7 | 0.99 (0.67–1.47) |
Hu et al. (2014) [14] | 2.6 | 1.9 | 0.62 (0.47–0.82) |
Ohki et al. (2015) [6] | 6.3 | 3.5 | 0.38 (0.22–0.63) |
Yao et al. (2015) [12] | 10.2 | 6.7 | 0.403 (0.251–0.646) |
Zhang et al. (2016) [49] | 4.9 (3.7–6.0) | 2.4 (1.3–3.4) | NA |
Authors (year) | Combination group (95% CI)/months | TACE alone group (95% CI)/months | HR (95% CI) |
---|---|---|---|
Kudo et al. (2011) [15] | 29.7 (28.6-NA) | NA | 1.06 (0.69–1.64) |
Lencioni et al. (2012) [10] | NA | NA | 0.898 (0.606–1.33) |
Qu et al. (2012) [45] | 27 (21.9–32.1) | 17 (8.9–25.0) | NA |
Bai et al. (2013) [46] | 7.5 | 5.1 | 0.61 (0.423–0.884) |
Muhammad et al. (2013) [47] | 20.6 (13.4–38.4) | 18.3 (11.8–32.9) | 0.82 (0.38–1.77) |
Hu et al. (2014) [14] | 7.0 | 4.9 | 0.63 (0.48–0.84) |
Ohki et al. (2015) [6] | 28.7 | 15.6 | 0.43 (0.24–0.76) |
Yao et al. (2015) [12] | 21.7 | 11.5 | 0.449 (0.302–0.668) |
Wan et al.(2016) [50] | 20.23 | 13.97 | 0.75 (0.61–0.94) |
Zhang et al. (2016) [49] | 14.9 (6.8–23.0) | 6.1 (4.0–8.1) | NA |
Varghese et al. (2017) [13] | BCLC-B = 16 (12.9–19.1) | BCLC-B = 9 (6.3–11.7) | BCLC-B:NA |
BCLC-C = 9 (6.8–11.2) | BCLC-C = 4(3–5) | BCLC-C:NA |
Relationship between aetiology and survival outcome
Authors (year) | Study design | Aetiology | Endpoint | HR |
---|---|---|---|---|
Kudo et al. (2011) [15] | RCT trial | HBV = 20% | TTP | 0.81(0.62–1.07) |
HCV = 60% | ||||
Bai et al. (2013) [46] | Comparative study | HBV = 87.9% | OS | 1.01(0.60–1.71) |
HCV = 4.9% | ||||
Muhammad et al. (2013) [47] | Comparative study | ST:HCV = 69% | OS | 1.04(0.66–1.63) |
DT:HCV = 93% | ||||
Zhao et al. (2013) [41] | Non-comparative study | HBV = 80% | OS | 1.372(0.773–2.437) |
HCV = 5% | ||||
Hu et al. (2014) [14] | Comparative study | ST:B = 82.9% | TTP | 1.01(0.76–1.34) |
T:B = 79.8% | ||||
Yao et al. (2016) [12] | Comparative study | ST:HBV = 84% | OS | 1.228(0.593–2.540) |
T:HBV = 83% | TTP | 0.878(0.494–1.561) |