Survival Benefit of Lenvatinib Plus PD-1 Inhibitor with or Without HAIC in Advanced Hepatocellular Carcinoma Beyond Oligometastasis: a Multicenter Cohort Study

Murong Wang,1,* Qunfang Zhou,2,* Hui Li,1 Mingyu Liu,3 Ruixia Li,4 Wei Wang,5 Xiaohui Wang,6 Jinhua Huang,1 Feng Duan2 1Department of Minimally Invasive Interventional Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong province, People’s Republic of China; 2Department of Interventional Radiology, 5th Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong province, People’s Republic of China; 4Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong province, People’s Republic of China; 5Department of General Surgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 6Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital, Changsha, Hunan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinhua Huang, Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong province, People’s Republic of China, Tel/Fax +86-020-87343272, Email [email protected] Feng Duan, Department of Interventional Radiology, 5th Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China, Tel/Fax +8610-66939123, Email [email protected]: The outcome between Lenvatinib plus programmed cell death protein-1 (PD-1) inhibitor and Lenvatinib in HCC beyond oligometastasis was unclear. In this multicenter, we compared the prognosis of Lenvatinib plus PD-1 inhibitor with Lenvatinib in HCC beyond oligometastasis.Patients and Methods: A total of 296 patients from six institutions were included. The patients were divided into two groups: (a) concurrent Lenvatinib plus PD-1 inhibitor treatment (Len+PD-1 group) and (b) Lenvatinib monotherapy (Len group). The primary endpoint was overall survival (OS), the second endpoint was progression-free survival (PFS) and efficacy.Results: The median OS was 20.1 ± 1.2 (17.7– 22.5) months and 15.7 ± 1.5 (12.8– 18.6) months in the Len+PD-1 and Len groups, respectively. The 12-, 24-, and 36-month OS rates were 79.1%, 39.4%, and 10.7% in the Len+PD-1 group, and 76.3%, 29.7%, and 0% in the Len group, respectively. The OS and PFS rates of the Len+PD-1 group were significantly longer compared with the Len group (hazard ratio [HR], 0.88; 95% confidence index [CI], 0.49– 0.94; P = 0.021) and (HR, 0.66; 95% CI, 0.50– 0.87; P = 0.003). A subgroup analysis revealed that OS (HR, 0.57; 95% CI, 0.36– 0.90; P = 0.016) was improved between the Len+PD-1 and Len groups with hepatic artery infusion chemotherapy (HAIC) treatment, whereas OS (HR, 1.11; 95% CI, 0.68– 1.80; P = 0.689) was similar between the Len and Len+PD-1 groups without HAIC.Conclusion: Lenvatinib combined with PD-1 inhibitor significantly improves the survival of HCC beyond oligometastasis. For patients with HAIC, there was obviously significance between Len and Len+PD-1 groups.Plain Language Summary: Lenvatinib as one of system therapy, is recommended treatment for HCC with multimetastases. The LEAP-002 trial, which evaluated Lenvatinib combined with Pembrolizumab exhibited improved progression-free survival (PFS) and overall survival (OS) compared with Lenvatinib alone. However, the combination efficacy on HCC beyond oligometastasis is unknown. In this multicenter study, we found that Lenvatinib combined with PD-1 inhibitor significantly improved both the OS and PFS and this combination could be recommended for HCC beyond oligometastases. OS and PFS were improved in the Len+PD-1 versus the Len group with hepatic artery infusion chemotherapy (HAIC) treatment, whereas the OS and PFS were similar between the Len and Len+PD-1 groups without HAIC. We provided clinical value that HAIC could be recommended as an effective local therapy to improve the prognosis for advanced HCC.Keywords: advanced hepatocellular carcinoma, Lenvatinib, beyond oligometastasis, prognosis, programmed death receptor-1 inhibitor