Combination of Bone-Modifying Agents with Immunotarget Therapy for Hepatocellular Carcinoma with Bone Metastases

Due to limited investigations about efficacy of tyrosine kinase inhibitors (TKIs) plus immune-checkpoint inhibitors (ICIs) versus TKIs alone, and effects of durations of bone modifying agents (BMAs) on the survival of patients with hepatocellular carcinoma (HCC) and bone metastases (BoM), we aim to compare the efficacy of TKIs both alone and in combination with ICIs, as well as comparing long-term and no or perioperative use of BMAs for patients with HCC and BoM. Patients with pathologically confirmed HCC and BoM were included in the study. They were stratified into the TKIs group and the TKIs + ICIs group, and the perioperative and the long-term use of BMAs group. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were calculated to assess the response to these regimes. The cumulative risk of initial skeletal-related events (SREs) was used to evaluate treatment efficacy for bone lesions. A total of 21 (33.9%) patients received TKIs (Sorafenib or Lenvatinib) alone and 41 (66.1%) received TKIs + ICIs. The combination group showed higher ORR than monotherapy group (1/21, 4.7% vs. 9/41, 22.0%; p = 0.1432); Additionally, the TKIs + ICIs group offered improved OS (18 months vs. 31 months; p = 0.015) and PFS (10 months vs. 23 months; p = 0.014), while this survival benefits were more profound in virus-infected patients than those non-infected. Prolonged OS (33 months vs. 16 months; p = 0.0048) and PFS (33 months vs. 11 months; p = 0.0027) were observed in patients with long-term use of BMAs compared with no or perioperative use of BMAs. The TKIs + ICIs combination and long-term adjuvant of BMAs may offer a survival advantage for HCC patients with BoM without severe adverse events, which requires further validations.