Multicenter, retrospective GUIDANCE001 study comparing transarterial chemoembolization with or without tyrosine kinase and immune checkpoint inhibitors as conversion therapy to treat unresectable hepatocellular carcinoma: Survival benefit in intermediate or advanced, but not early, stages

BACKGROUND AND AIMS: Various conversion therapy options have become available to patients with unresectable HCC, but which conversion therapy is optimal for which type of patient is controversial. This study compared the efficacy and safety of TACE alone or combined with immune checkpoint and tyrosine kinase inhibitors. APPROACH AND RESULTS: Data were retrospectively compared for patients with initially unresectable HCC who underwent conversion therapy consisting of TACE alone (n=459) or combined with immune checkpoint and tyrosine kinase inhibitors (n=343). Compared to the group that received TACE alone, the group that received triple conversion therapy showed significantly higher rates of overall survival (HR 0.43, 95%CI 0.35-0.53). In addition, triple therapy was associated with significantly longer median progression-free survival (15.9 vs. 8.0 mo, p <0.001). These results were confirmed in matched subsets of patients from each group. However, subgroup analysis confirmed the results only for patients with HCC in intermediate or advanced stages, not in an early stage. Those who received triple conversion therapy had a significantly higher rate of hepatectomy after conversion therapy (36.4 vs. 23.5%, p <0.001). Among those who underwent hepatectomy after conversion therapy, triple therapy was associated with a significantly higher rate of complete tumor response (32.1 vs. 11.1%, p <0.001). However, it was also associated with a significantly higher frequency of serious adverse events (35.6 vs. 27.0%, p =0.009). CONCLUSIONS: Combining TACE with immune checkpoint and tyrosine kinase inhibitors was associated with significantly better survival and conversion efficacy than TACE alone among patients with intermediate or advanced unresectable HCC.