Efficacy and Safety of TKI Plus PD-1 Inhibitors in Elderly uHCC Patients: A Retrospective Study

Abstract

Bowen Chen1,2 *, Jin Lei1,3 *, Haitao Zhao,4 Jinghui Dong,5 Zhen Zeng,1 Yinyin Li,1 Lingxiang Yu,1 Lin Zhou,6 Aiying Jia,5 Yinying Lu,1– 3 Jiamin Cheng1 1Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 2Peking University 302 Clinical Medical School, Beijing, People’s Republic of China; 3Guizhou Medical University Clinical Medical School, Guiyang, People’s Republic of China; 4Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 5Radiology Department, The Fifth Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 6Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiamin Cheng; Yinying Lu, Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, No. 100, Middle Road of the West 4th Ring, Beijing, 100039, People’s Republic of China, Tel [phone], Email [email protected]; [email protected]: To explore the efficacy and safety of sorafenib- or lenvatinib-based combination therapy with PD-1 inhibitors in elderly patients aged ≥ 75 years with unresectable hepatocellular carcinoma (uHCC).Patients and Methods: Systemic therapy-naïve uHCC patients who received first-line sorafenib- or lenvatinib-based combination therapy with PD-1 inhibitors were continually reviewed. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) in accordance with the Response Evaluation Criteria in Solid Tumors version 1.1. Adverse events (AEs) and immune-related AEs (irAEs) were also evaluated. Groups and subgroups were separated at the ages of 65 and 75 years and compared with 1:1 matching.Results: Total 169 eligible patients were enrolled, including 24 aged ≥ 75 years. Median progression-free survival (PFS) and overall survival (OS) in these 24 elderly patients were 4.6 (95% CI: 2.6– 6.6) months, and 17.0 (95% CI: 11.2– 22.8) months, with 3-, 6-, 12-month OS rate at 82.90%, 73.70%, and 57.50%. Age ≥ 75 years was confirmed to be a risk factor influencing PFS among patients aged ≥ 65 years. Adverse events (AEs) were recorded in all these 24 elderly patients, with seven patients experiencing immune-mediated AEs (irAEs). Nearly 30% of elderly patients stopped treatment due to AEs (16% of these due to irAEs). No statistical differences were found in all efficacy endpoints at the cutoff age of 65 years.Conclusion: For patients aged ≥ 75 years, application of PD-1 inhibitors in combination with sorafenib or lenvatinib is promising, but this has to be done with caution and needs to be confirmed by future prospective studies.Keywords: hepatocellular carcinoma, elderly, PD-1 inhibitors, efficacy, safety

Keywords

• hepatocellular carcinoma
• elderly
• pd-1 inhibitors
• efficacy
• safety