National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China.
Beijing Shenogen Biomedical Ltd, Beijing, China.
BMC Cancer. 2019 Mar 28;19(1):279. doi: 10.1186/s12885-019-5471-1.
With poor prognosis and limited treatment options for advanced hepatocellular carcinoma (HCC), development of novel therapeutic agents is urgently needed. This single-arm phase I study sought to assess the safety and preliminary efficacy of icaritin in human as a potential oral immunotherapy in addition to the immune-checkpoint inhibitors.
Eligible advanced HCC patients with Child-Pugh Class A or B were administered with a fixed oral dose of icaritin at either 600 or 800 mg b.i.d. The primary endpoint was safety, and the secondary endpoints included time-to-progression (TTP), overall survival (OS) and the clinical benefit rate (CBR). Icaritin treatment induced immune biomarkers and immune-modulating activities in myeloid cells were also explored.
No drug-related adverse events ≥ Grade 3 were observed in all 20 enrolled HCC patients. Among the 15 evaluable patients, 7 (46.7%) achieved clinical benefit, representing one partial response (PR, 6.7%) and 6 stable disease (SD, 40%). The median TTP was 141 days (range: 20-343 days), and the median OS was 192 days (range: 33-1036 days). Durable survival was observed in PR/SD patients with a median OS of 488 days (range: 72-773). TTP was significantly associated with the dynamic changes of peripheral neutrophils (p = 0.0067) and lymphocytes (p = 0.0337). Icaritin treatment induced changes in immune biomarkers-and immune-suppressive myeloid cells were observed.
Icaritin demonstrated safety profiles and preliminary durable survival benefits in advanced HCC patients, which were correlated with its immune-modulation activities and immune biomarkers. These results suggested the potential of icaritin as a novel oral immunotherapy for advanced HCC in addition to antibody-based PD-1/PD-L1 blockade therapies.
Clinicaltrial.gov identifier. NCT02496949 (retrospectively registered, July 14, 2015).
晚期肝细胞癌（HCC）预后差，治疗选择有限，因此迫切需要开发新的治疗药物。这项单臂 I 期研究旨在评估淫羊藿次苷在人类中的安全性和初步疗效，作为免疫检查点抑制剂的附加免疫治疗。
入组的晚期 HCC 患者，Child-Pugh 分级为 A 或 B，接受固定剂量的淫羊藿次苷口服，600 或 800mg，每日两次。主要终点为安全性，次要终点包括无进展生存期（TTP）、总生存期（OS）和临床获益率（CBR）。还探索了淫羊藿次苷治疗对髓样细胞免疫生物标志物和免疫调节活性的影响。
所有 20 例入组的 HCC 患者均未观察到与药物相关的≥3 级不良事件。在可评估的 15 例患者中，7 例（46.7%）达到临床获益，包括 1 例部分缓解（PR，6.7%）和 6 例疾病稳定（SD，40%）。中位 TTP 为 141 天（范围：20-343 天），中位 OS 为 192 天（范围：33-1036 天）。PR/SD 患者的生存时间持久，中位 OS 为 488 天（范围：72-773 天）。TTP 与外周中性粒细胞（p=0.0067）和淋巴细胞（p=0.0337）的动态变化显著相关。观察到淫羊藿次苷治疗引起免疫生物标志物和免疫抑制性髓样细胞的变化。
淫羊藿次苷在晚期 HCC 患者中显示出安全性和初步持久的生存获益，这与它的免疫调节活性和免疫生物标志物相关。这些结果表明，淫羊藿次苷可能成为晚期 HCC 的一种新型口服免疫疗法，与基于抗体的 PD-1/PD-L1 阻断治疗相结合。
Clinicaltrial.gov 标识符。NCT02496949（回顾性注册，2015 年 7 月 14 日）。
