Jinbin Chen1,2, Peiyao Xiong1,2, Man Nie1,3, Yangxun Pan1,2, Juncheng Wang1,2, Dandan Hu1,2, Zhongguo Zhou1,2, Yaojun Zhang1,2, Minshan Chen1,2, Li Xu4,5. 1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China. 2. Department of Liver Surgery, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Guangzhou, 510060, Guangdong, China. 3. Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, China. 4. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China. xuli@sysucc.org.cn. 5. Department of Liver Surgery, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Guangzhou, 510060, Guangdong, China. xuli@sysucc.org.cn.
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.
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.
Authors: Lihua E Budde; Sarit Assouline; Laurie H Sehn; Stephen J Schuster; Sung-Soo Yoon; Dok Hyun Yoon; Matthew J Matasar; Francesc Bosch; Won Seog Kim; Loretta J Nastoupil; Ian W Flinn; Mazyar Shadman; Catherine Diefenbach; Carol O'Hear; Huang Huang; Antonia Kwan; Chi-Chung Li; Emily C Piccione; Michael C Wei; Shen Yin; Nancy L Bartlett Journal: J Clin Oncol Date: 2021-12-16 Impact factor: 44.544