O-5 Outcomes by baseline liver function in patients with unresectable hepatocellular carcinoma treated with tremelimumab and durvalumab in the phase 3 HIMALAYA study

Immunotherapy in hepatocellular carcinoma: How does underlying liver disease influence therapeutic strategy and outcomes?

“…Besides the use of modified ALBI grade consisting in dichotomizing grade 2 patients in grade 2a and 2b (2a: > −2.60 to ≤ −2.270; 2b: > −2.270 to ≤ −1.39) did not allow significant differences between two subgroups 33 . In HIMALAYA trial, despite a benefit of DurvaTreme over sorafenib in the global cohort, subgroup analyses according to ALBI grades did not found any significant difference between DurvaTreme and sorafenib arms in both ALBI grade 1 ( n = 420; HR = 0.79; 95% CI, 0.62, 1.01) and grade 2 patients ( n = 361; HR = 0.83; 95% CI, 0.65, 1.05) probably due to a lack of statistical power 34 . Even though most clinical trials only integrate Child‐Pugh liver function and Eastern Cooperative Oncology Group (ECOG) performance status as patient stratification factors, ALBI should also be considered as a stratification factor for future RCTs and for improved treatment decision‐making.…”

Predictive Biomarkers for Immune-Checkpoint Inhibitor Treatment Response in Patients with Hepatocellular Carcinoma

“…According to the Imbrave150 exploratory analysis [210], the response to atezolizumab/bevacizumab was better than the response to sorafenib in patients with ALBI grade 1 compared to patients with ALBI grade 2. A subgroup analysis of the HIMALAYA trial [7] demonstrated that durvalumab/tremelimumab was superior to sorafenib in patients with ALBI grades 1 and 2; however, this difference did not reach statistical significance. In real-world data [211], baseline ABLI is considered an independent predictive biomarker in patients with HCC treated with immunotherapy.…”

“…Systemic treatment including immunotherapy is recommended for BCLC-C. For patients with BCLC-B, an intermediate stage of disease, TACE is the preferred option and immunotherapy is considered an appropriate option for those with a larger tumor burden. Most recent phase III studies [5,7,[212][213][214][215] on immunotherapy in HCC have focused on patients with BCLC-B and BCLC-C HCC. However, immunotherapy was reported to be effective in patients with BCLC-C HCC but not BCLC-B HCC compared to a control group (predominantly comprising patients treated with sorafenib), which could be due to underpowered analysis with a smaller sample size [5,7].…”

“…Most recent phase III studies [5,7,[212][213][214][215] on immunotherapy in HCC have focused on patients with BCLC-B and BCLC-C HCC. However, immunotherapy was reported to be effective in patients with BCLC-C HCC but not BCLC-B HCC compared to a control group (predominantly comprising patients treated with sorafenib), which could be due to underpowered analysis with a smaller sample size [5,7].…”

“…This upregulation of checkpoint proteins suggests that ICIs may be effective in HCC. The use of immunotherapy alone or in combination with targeted agents results in improved survival with a durable response and has become the new standard of care with several successful phase 3 studies published since 2020 [5][6][7]. However, despite these inspiring results, since HCC is a heterogeneous disease with diverse immunological characteristics, immunotherapy does not guarantee a clinical benefit in all patients with HCC, and more than two-thirds of advanced cancer patients do not respond to immunotherapy [8,9].…”