Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Clin Cancer Res. 2023 Sep 15;29(18):3650-3658. doi: 10.1158/1078-0432.CCR-23-0581.
Synergistic effect of radiotherapy and immunotherapy for the treatment of hepatocellular carcinoma (HCC) has been reported. This phase I/IIa pilot trial evaluated preliminary efficacy and safety of combination of radioembolization with yttrium-90 microspheres (Y90-radioembolization) and durvalumab in patients with locally advanced unresectable HCC.
Patients with Child-Pugh score ≤ 7 and locally advanced HCC, defined as Barcelona Clinic Liver Cancer (BCLC) stage B HCC or BCLC-C disease without extrahepatic metastases, received Y90-radioembolization followed by intravenous durvalumab 1,500 mg 7 to 14 days after Y90-radioembolization and every 4 weeks thereafter. Primary endpoint was time to progression (TTP) assessed by modified RECIST (mRECIST). Secondary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) determined by mRECIST, and safety.
All 24 patients enrolled received Y90-radioembolization and 23 received at least one dose of durvalumab. Median follow-up duration was 19.0 months (range, 2.2-24.2). Median TTP was 15.2 months [95% confidence interval (CI), 6.1-not estimated]. Median OS was not reached and 18-month OS rate was 58.3% (95% CI, 36.4-75.0). Median PFS was 6.9 months (95% CI, 5.4-15.2). Seven (29.2%) patients had a complete response and 13 (54.2%) had a partial response; ORR was 83.3% (95% CI, 62.6-95.3). Eleven (47.8%) patients experienced any-grade treatment-related adverse events. Two (8.7%) patients had grade 3 treatment-related adverse events (neutropenia and fever). None experienced any treatment-related serious adverse events.
In patients with locally advanced unresectable HCC, the combination of Y90-radioembolization and durvalumab demonstrated promising efficacy and safety, warranting further evaluation in large-scale controlled trials.
已有报道称放射治疗和免疫治疗联合用于治疗肝细胞癌（HCC）具有协同作用。本Ⅰ/Ⅱa 期试验评估了钇-90 微球（Y90-放射栓塞）联合 durvalumab 治疗局部晚期不可切除 HCC 患者的初步疗效和安全性。
患者的 Child-Pugh 评分≤7，局部晚期 HCC，定义为巴塞罗那临床肝癌（BCLC）分期 B HCC 或 BCLC-C 疾病且无肝外转移，接受 Y90-放射栓塞治疗，然后在 Y90-放射栓塞后 7-14 天静脉注射 durvalumab 1500mg，此后每 4 周 1 次。主要终点是通过改良 RECIST（mRECIST）评估的无进展生存期（TTP）。次要终点包括总生存期（OS）、无进展生存期（PFS）、mRECIST 确定的客观缓解率（ORR）和安全性。
所有 24 例患者均接受了 Y90-放射栓塞治疗，23 例患者至少接受了 1 剂 durvalumab治疗。中位随访时间为 19.0 个月（范围，2.2-24.2）。中位 TTP 为 15.2 个月[95%置信区间（CI），6.1-未估计]。中位 OS 未达到，18 个月 OS 率为 58.3%（95%CI，36.4-75.0）。中位 PFS 为 6.9 个月（95%CI，5.4-15.2）。7 例（29.2%）患者完全缓解，13 例（54.2%）患者部分缓解；ORR 为 83.3%（95%CI，62.6-95.3）。11 例（47.8%）患者发生任何级别治疗相关不良事件。2 例（8.7%）患者发生 3 级治疗相关不良事件（中性粒细胞减少和发热）。无治疗相关严重不良事件发生。
在局部晚期不可切除 HCC 患者中，Y90-放射栓塞联合 durvalumab 显示出有前景的疗效和安全性，值得进一步在大规模对照试验中进行评估。
