■局部治疗联合全身治疗作为不可切除的肝细胞癌（uHCC）的转换治疗的协同作用尚不清楚。这项研究的目的是评估经导管动脉化疗栓塞术（TACE）联合lenvatinib和camrelizumab（TACELENCAM）作为uHCC转换疗法的疗效和安全性。
■这种单臂，多中心,前瞻性研究在中国9家医院进行。患者（年龄18-75岁）诊断为uHCC，东部肿瘤协作组的表现评分（ECOG-PS）为0-1，Child-PughA级接受了卡姆雷珠单抗（200mg，每3周一次）和TACE治疗后的lenvatinib（体重≥60kg：12mg/天；<60kg：8mg/天）。在评估肿瘤符合切除标准后进行手术。不符合手术标准的患者继续接受三联疗法，直到疾病进展或无法耐受的毒性。主要终点是根据改良的实体瘤反应评估标准（mRECIST）和安全性的客观反应率（ORR）。次要终点包括手术转换率，根治性（R0）切除率，疾病控制率（DCR）。本研究在中国临床试验注册中心(ChiCTR2100050410)注册。
■在2021年10月25日至2022年7月20日之间，招募了55名患者。截至2023年6月1日数据截止，中位随访时间为13.3个月（IQR10.6-15.9个月）。三联疗法的最佳肿瘤反应是9例（16.4%）患者的完全反应（CR），部分缓解(PR)33例(60.0%),5例(9.1%)患者病情稳定(SD)，或进行性疾病（PD）在7（12.7％）患者。ORR为76.4%(42/55，95%CI，65.2-87.6%)，每mRECIST的DCR为85.5%(47/55,95%CI,76.2-94.8%)。55名患者中有24名（43.6％）患有3-4级治疗相关不良事件（TRAE）。没有发生5级TRAE。共有30例（30/55，54.5％）患者被转换为可切除的HCC，29例（29/55，52.7％）患者接受了切除术。R0切除率为96.6%(28/29)。手术人群的主要病理反应（MPR）和病理完全缓解（pCR）率分别为65.5％（19/29）和20.7％（6/29）。分别。只有一名患者出现了Clavien-DindoIIIa并发症（腹部感染）。无Clavien-DindoIIIb-V并发症发生。未达到中位OS和中位PFS。
■三联疗法（TACE+LEN+CAM）有望有效用于uHCC，具有可控的安全性。此外，三联疗法具有良好的转换效率，转换治疗后的手术是可行和安全的。为了阐明在三联疗法后接受手术治疗的uHCC患者是否比仅接受三联疗法的患者获得更好的生存益处，需要精心设计的随机对照试验.
■本研究由福建省自然科学基金资助,中国(2022J01691)和福建省卫生科技青年基金项目,中国(2022QNA035)。
UNASSIGNED: The synergistic effect of locoregional therapy in combination with systemic therapy as a conversion therapy for unresectable hepatocellular carcinoma (uHCC) is unclear. The purpose of this study was to evaluate the efficacy and safety of transcatheter arterial chemoembolisation (TACE) combined with lenvatinib and camrelizumab (TACE + LEN + CAM) as conversion therapy for uHCC.
UNASSIGNED: This single-arm, multicentre, prospective study was conducted at nine hospitals in China. Patients (aged 18-75 years) diagnosed with uHCC, an Eastern Cooperative Oncology Group performance score (ECOG-PS) of 0-1 and Child-Pugh class A received camrelizumab (200 mg, every 3 weeks) and lenvatinib (bodyweight ≥60 kg: 12 mg/day; <60 kg: 8 mg/day) after TACE treatment. Surgery was performed after tumour was assessed as meeting the criteria for resection. Patients who did not meet the criteria for surgery continued to receive triple therapy until disease progression or intolerable toxicity. Primary endpoints were objective response rate (ORR) according to the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and safety. Secondary endpoints included the surgical conversion rate, radical (R0) resection rate, and disease control rate (DCR). This study was registered with Chinese Clinical Trial Registry (ChiCTR2100050410).
UNASSIGNED: Between Oct 25, 2021, and July 20, 2022, 55 patients were enrolled. As of the data cutoff on June 1, 2023, the median follow-up was 13.3 months (IQR 10.6-15.9 months). The best tumour response to triple therapy was complete response (CR) in 9 (16.4%) patients, partial response (PR) in 33 (60.0%) patients, stable disease (SD) in 5 (9.1%) patients, or progressive disease (PD) in 7 (12.7%) patients. The ORR was 76.4% (42/55, 95% CI, 65.2-87.6%), and the DCR was 85.5% (47/55, 95% CI, 76.2-94.8%) per mRECIST. Twenty-four (43.6%) of the 55 patients suffered from grade 3-4 treatment-related adverse events (TRAEs). No grade 5 TRAEs occurred. A total of 30 (30/55, 54.5%) patients were converted to resectable HCC and 29 (29/55, 52.7%) patients underwent resection. The R0 resection rate was 96.6% (28/29). The major pathologic response (MPR) and pathologic complete response (pCR) rates in the surgery population were 65.5% (19/29) and 20.7% (6/29), respectively. Only one patient developed a Clavien-Dindo IIIa complication (abdominal infection). No Clavien-Dindo IIIb-V complications occurred. The median OS and median PFS were not reached.
UNASSIGNED: The triple therapy (TACE + LEN + CAM) is promising active for uHCC with a manageable safety. Moreover, triple therapy has good conversion efficiency and the surgery after conversion therapy is feasible and safe. To elucidate whether patients with uHCC accepting surgical treatment after the triple therapy can achieve better survival benefits than those who receive triple therapy only, well-designed randomised controlled trials are needed.
UNASSIGNED: This study was funded by the Natural Science Foundation of Fujian Province, China (2022J01691) and the Youth Foundation of Fujian Province Health Science and Technology Project, China (2022QNA035).
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