Table 1:
Outcomes from included studies on other systemic treatments versus sorafenib
| Study | Treatment allocation | N (evaluated) | Median OS (months) | Median TTP (months) | Median PFS (months) | ORR No. (%) | Terminated early? |
|---|---|---|---|---|---|---|---|
| Single drugs vs. sorafenib alone | |||||||
| Linifanib vs. sorafenib | |||||||
| Cainap, 2015 (12) | Linifanib | 514 (510) | 9.1 | 5.4 | 4.2 | 10.1% | Yes, for futility |
| Sorafenib | 521 (519) | 9.8 | 4.0 | 2.9 | 6.1% | ||
| HR 1.046; 95% CI 0.896–1.221; p = ns | HR 0.759; 95% CI 0.643–0.895; p = 0.001 | HR 0.813; 95% CI 0.697–0.948; p = 0.008 | p = 0.018 | ||||
| Lenvatinib vs. sorafenib | |||||||
| Kudo, 2018 (13) | Lenvatinib | 478 | 13.6 | 8.9 | 7.4 | 115 (24) | No |
| Sorafenib | 476 | 12.3 | 3.7 | 3.7 | 44 (9) | ||
| HR 0.92; 95% CI 0.79–1.06; p = NR | HR 0.63; 95% CI 0.53–0.73; p <0.0001 | HR 0.66; 95% CI 0.57–0.77; p <0.0001 | p <0.0001 | ||||
| Han, 2017 (14), abstract | HBV-positive participants | ||||||
| Lenvatinib | 259 | 13.4 | |||||
| Sorafenib | 244 | 10.2 | |||||
| HR 0.83; 95% CI 0.68–1.02; p = NR | |||||||
| HBV-positive Asia-Pacific participants | |||||||
| Lenvatinib | 218 | 13.1 | |||||
| Sorafenib | 208 | 9.4 | |||||
| HR 0.82; 95% CI 0.66–1.02; p = NR | |||||||
| Sunitinib vs. sorafenib | |||||||
| Cheng, 2013 (18) | Sunitinib | 530 | 7.9 | 4.1 | 3.6 | NR | Yes, for futility and safety |
| Sorafenib | 544 | 10.2 | 3.8 | 3.0 | |||
| HR 1.30; 95% CI 1.13–1.50; p = 0.9990 | HR 1.13; 95% CI 0.98–1.31; p = 0.8312 | HR 1.13; 95% CI 0.99–1.30; p = 0.8785 | |||||
| Nintedanib vs. sorafenib | |||||||
| Yen, 2018 (19) | Nintedanib | 63 | 10.2 | 2.8 | 2.7 | NR | No |
| Sorafenib | 32 | 10.7 | 3.7 | 3.7 | |||
| HR 0.94; 95% CI 0.59–1.49; p = NR | HR 1.21; 95% CI 0.73–2.01; p = NR | HR 1.19; 95% CI 0.73–1.93; p = NR | |||||
| Palmer, 2015 (20), abstract | Nintedanib | 62 | 11.9 | 5.5 (investigator assessed) | NR | NR | No |
| Sorafenib | 31 | 11.4 | 3.8 (investigator assessed) | ||||
| HR 0.88; 95% CI 0.52–1.47; p = NR | HR 1.05; 95% CI 0.63–1.76; p = NR | ||||||
| Brivanib vs. sorafenib | |||||||
| BRISK-FL, 2013 (21) | Brivanib | 577 (575) | 9.5 | 4.2 | NR | 12% | No |
| Sorafenib | 578 (575) | 9.9 | 4.1 | 9% | |||
| HR 1.07; 95% CI 0.94–1.23; p = 0.3116 | HR 1.01; 95% CI 0.88–1.16; p = 0.8532 | p = 0.569 | |||||
| Capecitabine vs. sorafenib | |||||||
| Wahab, 2012 (22), abstract | Capecitabine | N total | 5.07 | NR | 4 | 3.0% | No |
| Sorafenib | 52 | 7.05 | 6 | 14.5% | |||
| p <0.016 | p <0.005 | p = NR | |||||
| Nivolumab vs. sorafenib | |||||||
| Yau, 2019 (23), abstract | Nivolumab | 371 | 16.4 | NR | 3.7 | 57 (15) | No |
| Sorafenib | 372 | 14.7 | 3.8 | 26 (7) | |||
| HR 0.85; 95% CI 0.72–1.02; p = 0.0752 | p = NR | p = NR | |||||
| Drug combinations vs. sorafenib alone | |||||||
| Atezolizumab + bevacizumab vs. sorafenib | |||||||
| Nivolumab vs. sorafenib | |||||||
| Finn, 2020 (24) | Atezolizumab + bevacizumab | 336 | NE | 6.8 | 27% | No | |
| Sorafenib | 165 | 13.2 | 4.3 | 12% | |||
| HR 0.58; 95% CI 0.42–0.79; p <0.001 | HR 0.059; 95% CI 0.47–0.76; p <0.001 | p <0.001 | |||||
| Doxorubicin + sorafenib vs. sorafenib | |||||||
| Soradox trial, 2015 (25), abstract | Doxorubicin + sorafenib | 15 (11) | 6.97 | 7.11 | NR | NR | No |
| Sorafenib | 15 (12) | 19.8 | 8.45 | ||||
| p = 0.14 | p = 0.96 | ||||||
| CALGB 80802, 2019 (26) | Doxorubicin + sorafenib | 180 | 9.3 | 4.7 | 4.0 | 15 (10) | Yes, for futility |
| Sorafenib | 176 | 9.4 | 4.2 | 3.7 | 8 (5.4) | ||
| HR 1.03; 95% CI 0.82–1.29; p = 0.83 | HR 0.92; 95% CI 0.71–1.18; p = 0.49 | HR 0.93; 95% CI 0.75–1.16; p = 0.54 | p = ns | ||||
| GEMOX + sorafenib vs. sorafenib | |||||||
| GONEXT trial, 2019 (27) | GEMOX + sorafenib | 48 (40) | 13.5 | 6.2 | 6.2 | 6 (15) | No |
| Sorafenib | 46 (38) | 14.8 | 4.6 | 4.6 | 4 (9) | ||
| p = NR | p = NR | p = NR | p = NR | ||||
| Tigatuzumab + sorafenib vs. sorafenib | |||||||
| Cheng, 2015 (28) | Tigatuzumab (6/2mg/kg) + sorafenib | 53 (53) | 8.2 | 3.0 | NR | 5.7% | No |
| Tigatuzumab (6/6mg/kg) + sorafenib | 55 (54) | 12.2 | 3.9 | 14.8% | |||
| Sorafenib | 55 (55) | 8.2 | 2.8 | 10.9% | |||
| All pairwise comparisons; p = ns | All pairwise comparisons; p = ns | ||||||
| Mapatumumab + sorafenib vs. sorafenib + placebo | |||||||
| Ciuleanu, 2016 (29) | Mapatumumab + sorafenib | 50 | 10.0 | 4.1 | 3.2 | NR | No |
| Sorafenib + placebo | 51 | 10.1 | 5.6 | 4.2 | |||
| HR 1.195; 90% CI 0–1.651*; p = 0.7823 | HR 1.192; 95% CI 0–1.737; p = 0.7382 | HR 1.066; 90% CI 0–1.43*; p = NR | |||||
| Everolimus + sorafenib vs. sorafenib | |||||||
| Koeberle, 2016 (30) | Everolimus + sorafenib | 60 (50) | 12 | NR | 5.7 | 6 (10) | No |
| Sorafenib | 46 (43) | 10 | 6.6 | 0 (0) | |||
| p = NR | p = NR | p = NR | |||||
| AEG35256 + sorafenib vs. sorafenib | |||||||
| Lee, 2016 (31) | AEG35256 + sorafenib | 31 | 6.5 | NR | 4.0 | 3 (9.7) | No |
| Sorafenib | 17 | 5.4 | 2.6 | 0 (0.0) | |||
| Bevacizumab + erlotinib vs. sorafenib | |||||||
| Thomas, 2018 (32) | Bevacizumab + erlotinib | 47 | 8.6 | NR | NR | 15% | No |
| Sorafenib | 43 | 8.6 | 9% | ||||
| HR 0.92; 95% CI 0.57–1.47; p = NR | p = NR | ||||||
| Erlotinib + sorafenib vs. sorafenib + placebo | |||||||
| SEARCH, 2015 (33) | Erlotinib + sorafenib | 362 (362) | 9.5 | 3.2 | NR | 6.6% | No |
| Sorafenib + placebo | 358 (355) | 8.5 | 4.0 | 3.9% | |||
| HR 0.929; 95% CI 0.78–1.11; p = 0.408 | HR 1.135; 95% CI 0.94–1.37; p = 0.18 | p = 0.102 | |||||
| Pravastatin+sorafenib vs. sorafenib | |||||||
| Blanc, 2018 (34), abstract | Pravastatin+ sorafenib | 40 | 4.0 | NR | 3.4 | NR | No |
| Sorafenib | 41 | 3.8 | 3.2 | ||||
| p = NR | |||||||
| Resminostat + sorafenib vs. sorafenib | |||||||
| Tak, 2018 (35) | Resminostat + sorafenib | 86 (84) | 11.8 | 2.8 | NR | 3 (3.6) | No |
| Sorafenib | 84 (84) | 14.1 | 2.8 | 8 (9.5) | |||
| HR 1.046; 95% CI 0.70–1.55; p = 0.824 | HR 0.984; 95% CI 0.68–1.41; p = 0.925 | p = NR | |||||
| Tegafur–uracil (UFT) + sorafenib vs. sorafenib | |||||||
| Azim, 2018 (36) | UFT + sorafenib | 36 | 8.2 | 7.5 | 6 | NR | Yes, for futility |
| Sorafenib | 38 | 10.5 | 8.2 | 6 | |||
| HR 1.58; 95% CI 0.90– 2.76; p = 0.112 | HR 1.07; 95% CI 0.52–2.22; p = 0.855 | HR 1.19; 95% CI 0.71–2.01; p = 0.508 | |||||
*
Note this is a 90% confidence interval
OS = Overall survival; TTP = Time to progression; PFS = Progression-free survival; ORR = Objective response rate; HR = Hazard ratio; CI = Confidence interval; HBV = Hepatitis B virus; NR = Not reported; GEMOX = Gemcitabine/oxaliplatin; NE = Not estimable; ns = Not significant