Sequential HAIC-TACE combined with targeted and immunotherapy in hepatocellular carcinoma: a quality improvement study.

[BACKGROUND] Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality. Emerging evidence suggests that quadruple therapy - combining hepatic artery infusion chemotherapy (HAIC), transcatheter arterial chemoembolization (TACE), targeted therapy, and immunotherapy - improves outcomes. However, few studies have directly compared this regimen with triple therapy (TACE plus targeted therapy and immunotherapy), and the optimal sequence of locoregional treatments within this regimen remains unclear.

[OBJECTIVE] To compare the efficacy and safety of HAIC-first quadruple therapy, TACE-first quadruple therapy, and triple therapy in patients with unresectable HCC (uHCC).

[MATERIALS AND METHODS] We retrospectively analyzed 158 patients with uHCC who received: HAIC-first quadruple therapy (HTTI, n = 61), TACE-first quadruple therapy (THTI, n = 41), or triple therapy (TTI, n = 56). Tumor response was assessed with modified RECIST; progression-free survival (PFS), overall survival (OS), and safety were compared.

[RESULTS] The HTTI group achieved the highest objective response rate (ORR, 81.97%) and disease control rate (DCR, 96.72%), outperforming the THTI (ORR 73.17%, DCR 95.12%) and TTI groups (ORR 64.28%, DCR 85.71%). The median OS (mOS) was not reached in the HTTI group; the THTI group had a longer mOS (22.30 months) than the TTI group (19.00 months, P = 0.046). The median PFS (mPFS) was also longer in the HTTI group (12.90 months), compared to the THTI (10.40 months, P = 0.042) group and TTI groups (9.30 months, P < 0.001). Quadruple therapy increased grade 1 and 2 hypoalbuminemia, thrombocytopenia, and hand-foot syndrome, but grade 3 and 4 toxicities were similar across groups.

[CONCLUSION] Quadruple therapy demonstrates superior efficacy compared to triple therapy for uHCC. Initiating treatment with HAIC followed by TACE appears more effective than the reverse sequence and merits prospective validation.