Efficacy and Safety of Combined Targeted Therapy and Immunotherapy versus Targeted monotherapy in Unresectable Hepatocellular Carcinoma: A Systematic review and Meta- Analysis

Abstract

Abstract Background Cancer therapy has evolved from non-specific cytotoxic agents to a selective, mechanism-based approach, including targeted agents and immunotherapy. For unresectable hepatocellular carcinoma (HCC), though the response to targeted therapies is acceptable with the improved survival, the high tumor recurrence rate and drug-related side effects remain problematic. Given immune checkpoint inhibitor alone not robust enough to improve survival in unresectable HCC, growing evidence support the combination of targeted therapy and immunotherapy with synergistic effect. Methods Online databases including PubMed, EMBASE, Cochrane Library, and Web of Science were searched for the studies that compared targeted monotherapy with the combination therapy of targeted drug and checkpoint inhibitors in unresectable HCC patients. Eligibility criteria were the presence of at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST1.1) for unresectable HCC patients; Eastern Cooperative Oncology Group performance status of 0–2; Child-Pugh score ≤ 7. Outcome measurements include overall survival (OS), progression-free survival (PFS), and treatment-related adverse event (TRAE). Results Three phase II/III randomized controlled trials were included. The pooled results showed that the combination therapy had significantly better survival than targeted monotherapy, in terms of OS (HR = 0.67; 95% CI, 0.50–0.91) and PFS (HR = 0.58, 95% CI: 0.51–0.67), respectively. In the incidence of grade 3–5 TRAEs, the combination therapy was significantly higher than targeted monotherapy (OR = 1.98, 95% CI, 1.13–3.48). Conclusions For unresectable HCC, combined targeted drug and immunotherapy significantly improved survival compared to targeted monotherapy. However, the incidences of AEs of combinational therapy were higher than targeted monotherapy.