PD-1 inhibitors combined with tyrosine kinase inhibitors for conversion therapy in patients with unresectable hepatocellular carcinoma: a retrospective cohort study.

Background: The majority of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage, precluding surgical resection. Studies have evaluated the use of programmed cell death protein 1 (PD-1) monoclonal antibodies in combination with tyrosine kinase inhibitors (TKIs) for conversion of unresectable intermediate-to-advanced HCC into resectable disease. However, the success rate of conversion therapy in these studies remains unsatisfactory. This study aimed to evaluate the real-world efficacy and safety of TKIs combined with PD-1 inhibitors as conversion therapy for patients with unresectable HCC, specifically focusing on conversion success rates and long-term survival outcomes. Methods: This retrospective, single-center cohort study evaluated the efficacy and safety of combining TKIs with PD-1 inhibitors as conversion therapy in 63 patients with unresectable HCC treated at Xiangya Hospital between August 2018 and December 2023. Patients received TKIs and PD-1 inhibitors, with some also undergoing transarterial chemoembolization or hepatic arterial infusion chemotherapy. The primary outcome of the study was the rate of successful conversion. Other outcome measures evaluated were the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the safety profile of the treatment. Results: The ORR was 82.5% with the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and 63.5% with RECIST 1.1, and the conversion success rate was 60.3% (38/63). Among the patients, 27 underwent surgical resection or ablation, and the pathological complete response rate was 33.3%. The median PFS was 20.7 months for the overall cohort and was significantly prolonged to 41.23 months in patients with successful conversion. The median OS was not reached, and successful conversion was associated with a reduced risk of progression [hazard ratio (HR): 0.11; P<0.001] and death (HR: 0.10; P<0.001). Grade 3-4 adverse events occurred in 30.2% of patients and primarily consisted of increased transaminase levels and leukopenia. Conclusions: This study demonstrates that TKI combined with PD-1 inhibitors is an effective and tolerable conversion therapy for patients with unresectable HCC, with successful conversion significantly improving the survival outcomes. Further multicenter, randomized studies are needed to optimize treatment strategies and patient selection.