Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, People's Republic of China.
OrigiMed, Shanghai, People's Republic of China.
Oncologist. 2020 Jun;25(6):470-474. doi: 10.1634/theoncologist.2019-0563. Epub 2020 Feb 26.
We report on a patient with hepatocellular carcinoma (HCC) who developed bone metastasis after surgery. RET amplification, high tumor mutational burden (TMB; TMB ≥10 mutations per megabase), and programmed death-ligand 1 (PD-L1) expression were detected by next-generation sequencing. Oral administration of cabozantinib was initiated. Nivolumab was added after 1 month. The patient responded well to cabozantinib and nivolumab therapy, with tolerated adverse reactions, and achieved progression-free survival of more than 25 months. To the best of our knowledge, this is the first clinical case report in the literature to describe the benefit of cabozantinib and nivolumab treatment in a patient with HCC and RET amplification, high TMB, and positive PD-L1 expression. This study explored the selection of biomarkers for targeted therapy and combination immunotherapy in patients with HCC. KEY POINTS: A patient with metastatic hepatocellular carcinoma (HCC) harboring RET amplification, high tumor mutational burden, and positive programmed death-ligand 1 expression responded well to the combination of cabozantinib and nivolumab therapy with progression-free survival of longer than 25 months. The combination of nivolumab and cabozantinib may be a good option for patients with advanced HCC, especially those with bone metastasis. The efficacy of cabozantinib and immune checkpoint inhibitors suggests the necessity of the combined application of multiple detection technologies, including next-generation sequencing and immunohistochemistry, for patients with HCC. This study explored the selection of biomarkers for targeted therapy and combination immunotherapy for patients with HCC.
我们报告了一例肝癌（HCC）患者，该患者在手术后发生骨转移。通过下一代测序检测到 RET 扩增、高肿瘤突变负担（TMB；TMB≥10 个突变/兆碱基）和程序性死亡配体 1（PD-L1）表达。开始口服卡博替尼。1 个月后加入纳武利尤单抗。患者对卡博替尼和纳武利尤单抗治疗反应良好，不良反应可耐受，并实现了超过 25 个月的无进展生存期。据我们所知，这是文献中首例描述卡博替尼和纳武利尤单抗治疗 HCC 和 RET 扩增、高 TMB、PD-L1 阳性患者获益的临床病例报告。本研究探讨了 HCC 患者靶向治疗和联合免疫治疗的生物标志物选择。关键点：一名转移性肝癌（HCC）患者携带 RET 扩增、高肿瘤突变负担和 PD-L1 阳性表达，对卡博替尼和纳武利尤单抗联合治疗反应良好，无进展生存期超过 25 个月。纳武利尤单抗和卡博替尼的联合可能是晚期 HCC 患者，特别是有骨转移患者的一个不错选择。卡博替尼和免疫检查点抑制剂的疗效表明，对于 HCC 患者，有必要联合应用多种检测技术，包括下一代测序和免疫组织化学。本研究探讨了 HCC 患者靶向治疗和联合免疫治疗的生物标志物选择。
