Comparison of the efficacy and safety of TACE-HAIC-MTTs-ICIs and TACE-MTTs-ICIs in the hepatocellular carcinoma: a prognostic analysis based on the dynamic changes of serum AFP

Abstract

Background: To evaluate the efficacy and safety of two combination treatments for hepatocellular carcinoma (HCC): 1) transarterial chemoembolization (TACE) with hepatic arterial infusion chemotherapy (HAIC) combined with molecular targeted therapies (MTTs) and immune checkpoint inhibitors (ICIs) (TACE-HAIC-MI), and 2) TACE combined with MTTs and ICIs (TACE-MI). In addition, analysis of changes in serum AFP levels and patient survival was performed.

Methods: A retrospective study of 459 HCC patients treated with one of the aforementioned treatments was performed: TACE-MI ( N = 305) and TACE-HAIC-MI ( N = 154). Inverse probability of treatment weighting (IPTW) was used to minimize confounding factors, and sensitivity analyses were conducted. The joint latent class model was used to model AFP change trajectories, and Cox regression analysis was used to identify prognostic factors. Primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. Tumor response and adverse events (AEs) were assessed using RECIST v1.1 and CTCAE v5.0, respectively.

Results: After IPTW, the median OS of the TACE-HAIC-MI group was 23.9 months, and for the TACE-MI group it was 21.7 months( P = 0.432). The median PFS of the two groups was 9.77 months versus 8.97 months ( P = 0.45). Six optimal latent classes of AFP trajectories were identified. Class 1 demonstrated a median OS of 20.43 months, while class 2 did not reach the median OS. The median OS for class 3 was 43.87 months, for class 4 was 18.47 months, for class 5 was 8.13 months, and for class 6 was 11.37 months. Cox regression analyses showed that AFP trajectory independently predicted median OS and PFS, with HRs between 1.56 and 45.28. The most common AEs were elevated transaminase levels, electrolyte imbalances, anemia, and pain. Nausea and vomiting were more frequent in the TACE-HAIC-MI group, and elevated transaminase levels were less common than in the TACE-MI group.

Conclusion: TACE-HAIC-MI and TACE-MI treatments have no significant survival differences in patients with HCC. Patients with a favorable AFP response have significantly better survival outcomes than those with a poor response.

Keywords: AFP trajectory; HAIC; ICI; MTT; TACE; hepatocellular carcinoma; survival.

Figure 1.

The flowchart of patients. Abbreviations: TACE-MI, transarterial chemoembolization (TACE) combined with molecular targeted therapies (MTTs) and immune checkpoint inhibitors (ICIs); TACE-HAIC-MI, TACE with hepatic arterial infusion chemotherapy (HAIC) combined with MTTs and ICIs; BCLC, Barcelona Clinic Liver Cance.

Figure 2.

Analysis of survival, tumor response, and adverse events. OS(A) and PFS(B) between TACE-HAIC-MI and TACE-MI group before IPTW. OS(C) and PFS(D) between TACE-HAIC-MI and TACE-MI group after IPTW analysis. Tumor response of TACE-HAIC-MI and TACE-MI group(E). Incidence of adverse events for any grades (F), grade 1 or 2(G), and grade 3 or 4(H) between TACE-HAIC-MI and TACE-MI group. Abbreviations: OS, overall survival; PFS, progression-free survival; TACE-MI, transarterial chemoembolization (TACE) combined with molecular targeted therapies (MTTs) and immune checkpoint inhibitors (ICIs); TACE-HAIC-MI, TACE with hepatic arterial infusion chemotherapy (HAIC) combined with MTTs and ICIs. IPTW, inverse probability of treatment weighting. CR, complete response; PR, partial response; SD, stable disease; ORR, overall response rate; DCR, disease control rate.

Figure 3.

Class-specific predicted trajectory and weighted predictions.

Figure 4.

Analysis of OS(A) and PFS(B) for different classes in mj6a model. Abbreviations: OS, overall survival; PFS, progression-free survival.