Table 1.
Results of selected trials for first-line therapy in patients with advanced HCC.
| Study (Year) | Phase | N | Population | Geographical Region | Drug | Median Overall Survival | Median Progression-Free Survival | Objective Response Rate |
|---|---|---|---|---|---|---|---|---|
| REFLECT trial (2018) [31] |
III noninferiority | 954 | Unresectable HCC and no prior systemic therapy (99% Child-Turcotte-Pugh class A) |
29% (white); 69% (Asian); 2% (other) | Lenvatinib vs. sorafenib |
13.6 mo for lenvatinib vs. 12.3 mo for sorafenib (HR: 0.92, 95% CI: 0.79–1.06) |
7.4 mo for lenvatinib vs. 3.7 mo for sorafenib (HR: 0.66; p < 0.0001) |
24.1% for lenvatinib vs. 9.2% for sorafenib (p < 0.0001) |
| IMbrave 150 trial (2021) [32,33] |
III | 336 | Unresectable or metastatic HCC, Child-Pugh liver function score < 7, and no prior systemic therapy |
40% (Asians, excluding Japan); 60% (rest of the world) | Atezolizumab-bevacizumab vs. sorafenib | 19.2 mo for atezolizumab-bevacizumab vs. 13.4 mo for sorafenib (HR: 0.66; p < 0.001) |
6.9 mo for atezolizumab-bevacizumab vs. 4.3 mo for sorafenib (HR: 0.65; p < 0.001) |
30% to atezolizumab-bevacizumab vs. 11% to sorafenib |
| COSMIC-321 trial (2022) [34] |
III | 837 | Unresectable or metastatic HCC, Child-Pugh liver function score < 7, and no prior systemic therapy |
29.3% (Asians); 70.7% (Other) | Cabozantinib-atezolizumab vs. sorafenib | 15.4 mo for cabozantinib-atezolizumab vs. 15.5 mo for sorafenib (HR: 0.90, p = 0.44) | 6.8 mo for cabozantinib-atezolizumab vs. 4.2 mo for sorafenib (HR: 0.63, p = 0.0012) | 13% to cabozantinib-atezolizumab vs. 6% to sorafenib |
| HIMALAYA trial (2022) [35] |
III | 1171 | Unresectable HCC, Child-Pugh liver function score < 7, and no prior systemic therapy |
40.9% (Asians, excluding Japan); 59.1% (rest of the world) | Durvalumab-tremelimumab or durvalumab vs. sorafenib | 16.43 mo for STRIDE vs. 13.77 for sorafenib (HR: 0.78; p = 0.0035) |
3.78 mo for STRIDE and 3.65 mo for durvalumab vs. 4.07 for sorafenib (HR: 0.90; p = 0.0035 and HR: 1.02, p = 0.0674) |
20.1% to STRIDE, 17% to durvalumab vs. 5.1 to sorafenib |
| RATIONALE-301 trial (2022) [36] |
III | 674 | Unresectable or metastatic HCC, Child-Pugh liver function score < 7, and no prior systemic therapy |
63.1% (Asians, excluding Japan); 11.4 (Japan); 25.5% (rest of the world) | Tislelizumab vs. sorafenib | 15.9 mo for tislelizumab vs. 14.1 mo for sorafenib (HR: 0.8) | 2.2 mo for tislelizumab vs. 3.6 mo for sorafenib (HR: 1.1) | 14.3% to tislelizumab vs. 5.4% to sorafenib |
| CheckMate 459 (2019) [37] |
III | 743 | Unresectable Child-Pugh A HCC naïve to systemic treatment |
40% (Asian); 60% (United States, Canada or Europe) | Nivolumab vs. sorafenib |
16.4 mo for nivolumab vs. 14.7 mo for sorafenib (HR: 0.85; p = 0.0752) |
3.7 mo for nivolumab vs. 3.8 mo for sorafenib |
15% for nivolumab and 7% to sorafenib |
| CheckMate-040: cohort B (2021) [38] |
I/II | 49 | Unresectable or metastatic HCC, Child-Pugh liver function score B, with or without prior systemic therapy |
55% (Asian); 41% (white); 2% (black); 2% (other) | Nivolumab single arm | 9.8 mo for sorafenib naïve patients and 7.4 mo for previously treated patients | 3.4 mo for sorafenib naïve patients and 2.2 mo for previously treated patients | 12% |
| KEYNOTE-524 trial (2022) [39] |
Ib | 104 | Unresectable or metastatic HCC, Child-Pugh liver function score < 7, and no prior systemic therapy |
51% (white); 28% (Asian); 2% (black); 5% (other); 14% (missing) | Lenvatinib-pembrolizumab single arm | 22 mo | 9.3 mo per mRECIST; 8.6 per RECIST v1.1 | 46% per mRECIST; 36% per RECIST v1.1 |
| FOHAIC-1 (2021) [40] | III | 262 | Locally advanced or unresectable HCC with or without extrahepatic oligometastasis, Child-Pugh liver function score ≤ 7 |
HAIC (FOLFOX) vs. sorafenib |
13.9 mo for HAIC vs. 8.2 mo for sorafenib (HR: 0.408, p < 0.001) |
7.8 mo for HAIC vs. 4.3 mo for sorafenib (HR: 0.451, p < 0.001) |
31.5% to HAIC and 1.5% to sorafenib per RECIST; 35.4% to HAIC and 5.3% to sorafenib per mRECIST (p < 0.001) |
|
| LEAP-002 (2021) [41] | III | 794 | Primary treatment-naive HCC, non-amenable to curative therapy, Child-Pugh A | 30.7% (Asian without Japan) vs. 69.3% (western regions and Japan) | lenvantinib plus pembrolizumab vs. lenvantinib | 21.2 mo for lenvatinib and pembrolizumab vs. 19 mo for lenvatinib (HR: 0.84; p = 0.0227) | 8.2 mo for lenvatinib and pembrolizumab vs. 8.1 mo for lenvatinib (HR: 0.834; p = 0.0466) | 26.1% for lenvatinib and pembrolizumab and 17.5% for lenvatinib per RECIST 1.1; 40.6% for lenvatinib and pembrolizumab and 34.1% for lenvatinib per mRECIST |
| Qin, et al. (2022) [42] | III | 543 | Unresectable or metastatic HCC primary treatment naive, BCLC satage B, Child-Pugh A | 82.7% (Asian) vs. 17.3% (non-Asian) | Camrelizumab + rivoceranib vs. sorafenib | 22.1 mo for canrelizumab + rivoceranib vs. 15.2 mo for sorafenib (HR: 0.62; 95% CI: 0.49–0.80) | 5.6 mo for canrelizumab + rivoceranib vs. 3.7 mo for sorafenib (HR: 0.52; 95% CI: 0.41–0.65) | 25.4% for camrelizumab and rivoceranib and 5.9% for sorafenib per RECIST 1.1; 33.1% for camrelizumab and rivoceranib and 10% for sorafenib per mRECIST |
| LAUNCH (2022) [43] | 338 | Primary treatment-naive or initial recurrent advanced HCC after surgery without adjuvant treatment, Child-Pugh class A | 100% (Asian—China) | LEN-TACE vs. lenvatinib | 17.8 mo forLEN-TACE vs. 11.5 mo for lenvatinib (HR: 0.33; p < 0.001) |
10.6 mo forLEN-TACE vs. 6.4 mo for lenvatinib (HR: 0.36; p < 0.001) |
45.9% to LEN_TACE and 20.8% to lenvatinib per RECIST; 54.1% to LEN-TACE and 25% to lenvatinib per mRECIST (p < 0.001) |
Abbreviations: HCC: hepatocellular carcinoma; mo: months; HR: hazard ratio; RECIST: Response Evaluation Criteria in Solid Tumors; vs.: versus.