Chen Zhaoyu, Shen Zhilong, Wang Xiang, Wang Pengru, Zhu Xiaofei, Fan Jiefu, Li Bo, Xu Wei, Xiao Jianru
Department of Orthopedic Oncology, Changzheng Hospital, Naval Medical University (Second Military Medical University), 415 Fengyang Road, Shanghai 200003, China.
Department of Radiation Oncology, Changhai Hospital, Naval Medical University (Second Military Medical University), 168 Changhai Road, Shanghai 200082, China.
J Clin Med. 2022 Nov 23;11(23):6901. doi: 10.3390/jcm11236901.
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%; = 0.1432); Additionally, the TKIs + ICIs group offered improved OS (18 months vs. 31 months; = 0.015) and PFS (10 months vs. 23 months; = 0.014), while this survival benefits were more profound in virus-infected patients than those non-infected. Prolonged OS (33 months vs. 16 months; = 0.0048) and PFS (33 months vs. 11 months; = 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.
由于关于酪氨酸激酶抑制剂（TKIs）联合免疫检查点抑制剂（ICIs）与单独使用TKIs的疗效，以及骨改良剂（BMAs）使用时长对肝细胞癌（HCC）合并骨转移（BoM）患者生存影响的研究有限，我们旨在比较TKIs单独使用及与ICIs联合使用的疗效，同时比较HCC合并BoM患者长期使用与不使用或围手术期使用BMAs的情况。纳入研究的患者为经病理确诊的HCC合并BoM患者。他们被分为TKIs组、TKIs + ICIs组，以及围手术期和长期使用BMAs组。计算总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和疾病控制率（DCR）以评估对这些治疗方案的反应。采用初始骨相关事件（SREs）的累积风险来评估骨病变的治疗效果。共有21例（33.9%）患者单独接受TKIs（索拉非尼或仑伐替尼）治疗，41例（66.1%）患者接受TKIs + ICIs治疗。联合治疗组的ORR高于单药治疗组（1/21，4.7%对9/41，22.0%；P = 0.1432）；此外，TKIs + ICIs组的OS（18个月对31个月；P = 0.015）和PFS（10个月对23个月；P = 0.014）有所改善，而这种生存获益在病毒感染患者中比未感染患者更为显著。与不使用或围手术期使用BMAs相比，长期使用BMAs的患者观察到OS延长（33个月对16个月；P = 0.0048）和PFS延长（33个月对11个月；P = 0.0027）。TKIs + ICIs联合治疗及BMAs的长期辅助治疗可能为HCC合并BoM患者带来生存优势，且无严重不良事件，这需要进一步验证。
