Abstract
PURPOSE: Lenvatinib is recommended as a first-line therapy in unresectable hepatocellular carcinoma (HCC). Combination therapy with local therapy (LT) or PD-1/PD-L1 inhibitors (PI) might improve the antitumor effect of lenvatinib. The objective of this study was to investigate the antitumor effect of lenvatinib-based combination therapies. METHODS: The study retrospectively analyzed 215 HCC patients who received lenvatinib therapy. The outcomes of patients treated with lenvatinib monotherapy as well as combination strategies were compared. Progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 was the primary endpoint, while PFS by mRECIST, overall survival (OS), objective response rate (ORR) and safety were the secondary endpoints. Propensity score matching (PSM) analysis was performed to overcome the bias of baseline characteristics. RESULTS: Compared with lenvatinib monotherapy, combination therapy prolonged PFS (by RECIST v1.1, 7.77 vs. 4.43 months, P = 0.045; by mRECIST, 6.97 vs. 5.27 months, P = 0.067). A higher ORR was also recorded in the combined-therapy group, according to both RECIST v1.1 (37 vs. 5%, P < 0.001) and mRECIST (53 vs. 11%, P < 0.001). Similar outcomes were obtained after PSM. Moreover, triple therapy (combined with both PI and LT) was significantly superior to dual therapy (combined with either PI or LT) in terms of better PFS according to RECIST v1.1 (8.90 vs. 6.43 months, P = 0.023). However, adverse events occurred in more patients receiving combined therapy and triple therapy. No difference was observed in OS between groups. CONCLUSION: Combination therapies based on lenvatinib were associated with significantly better PFS and tumor response rates than lenvatinib monotherapy in HCC patients.