The First Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
University of Shanghai for Science and Technology, Shanghai, China.
Nat Commun. 2024 Oct 29;15(1):9350. doi: 10.1038/s41467-024-53704-5.
Hepatocellular carcinoma (HCC) patients with macrovascular invasion (MVI) have dismal prognosis and there are no standard perioperative therapies. This phase 2 trial (ChiCTR2000036385) aimed to investigate the activity and safety of perioperative tislelizumab plus intensity modulated radiotherapy (IMRT) for resectable HCC with MVI. Thirty treatment-naïve patients with MVI received 3 cycles of tislelizumab intravenously (200 mg, every three weeks) and concurrent IMRT (45 Gray in 15 fractions). Primary endpoints were the overall response rate (ORR) and overall survival (OS). Secondary endpoints were the proportion of patients with a complete or major pathological response (pCR or MPR), recurrence-free survival (RFS) and safety. Of patients enrolled, 15 (50%) underwent curative surgery followed by adjuvant tislelizumab. The ORR was 30.0% (90% CI 16.6%-46.5%) and the median OS was 18.7 months. Of the 15 patients underwent surgical resection, 10 (66.7%) achieved pCR or MPR and 8 (53.3%) remained recurrence-free. The median RFS were not reached with a median follow-up of 21.77 months (95% CI 12.50-31.03) post-surgery. 4 (13.3%) patients experienced grade 3 treatment-related adverse events. The most common events were thrombocytopenia, leukopenia, and anemia. The trial has met the pre-specified endpoints, and these results support further studies of perioperative immunotherapy plus radiotherapy in HCC.
肝细胞癌（HCC）伴大血管侵犯（MVI）患者预后极差，且尚无标准的围手术期治疗方法。本Ⅱ期临床试验（ChiCTR2000036385）旨在评估替雷利珠单抗联合调强放疗（IMRT）用于可切除伴 MVI 的 HCC 的疗效和安全性。30 例初治伴 MVI 的 HCC 患者接受 3 周期替雷利珠单抗静脉滴注（200mg，每 3 周 1 次）联合 IMRT（45Gy，15 次）。主要终点为总缓解率（ORR）和总生存期（OS）。次要终点为完全或主要病理缓解（pCR 或 MPR）率、无复发生存期（RFS）和安全性。入组患者中，15 例（50%）患者接受根治性手术，术后接受替雷利珠单抗辅助治疗。ORR 为 30.0%（90%CI 16.6%-46.5%），中位 OS 为 18.7 个月。在接受手术切除的 15 例患者中，10 例（66.7%）获得 pCR 或 MPR，8 例（53.3%）无复发。术后中位随访 21.77 个月（95%CI 12.50-31.03）时，中位 RFS 尚未达到。4 例（13.3%）患者发生 3 级治疗相关不良事件。最常见的事件为血小板减少、白细胞减少和贫血。该试验达到了预设终点，这些结果支持进一步研究围手术期免疫治疗联合放疗在 HCC 中的应用。
