Background: Combined therapy with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies has shown high tumor response rates for patients with unresectable hepatocellular carcinoma (HCC). However, using this treatment strategy to convert initially unresectable HCC to resectable HCC was not reported. Methods: Consecutive patients with unresectable HCC who received first-line therapy with combined TKI/anti-PD-1 antibodies were analyzed. Tumor response and resectability were evaluated via imaging every 2 months (±2 weeks) using RECIST v1.1. Resectability criteria were (1) R0 resection could be achieved with sufficient remnant liver volume and function; (2) intrahepatic lesions were evaluated as partial responses or stable disease for at least 2 months; (3) no severe or persistent adverse effects occurred; and (4) hepatectomy was not contraindicated. Results: Sixty-three consecutive patients were enrolled. Of them, 10 (15.9%) underwent R0 resection in 3.2 months (range: 2.4–8.3 months) after the initiation of combination therapy. At baseline, these 10 patients had a median largest tumor diameter of 9.3 cm, 7 had Barcelona Clinic Liver Cancer stage C (vascular invasion) disease, 2 had stage B, and 1 had stage A. Before surgery, 6 patients were evaluated as a partial response, 3 stable disease, and 1 partial response in the intrahepatic lesion but a new metastatic lesion in the right adrenal gland. Six patients (60%) achieved a pathological complete response. One patient died from immune-related adverse effects 2.4 months after hepatectomy. After a median follow-up of 11.2 months (range: 7.8–15.9 months) for other 9 patients, 8 survived without disease recurrence, and 1 experienced tumor recurrence. Conclusions: Combination of TKI/anti-PD-1 antibodies is a feasible conversion therapy for patients with unresectable HCC to become resectable. This study represents the largest patient cohort on downstaging role of combinational systemic therapy on TKI and PD-1 antibody for HCC.
Liver Cancer

中文翻译：

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酪氨酸激酶抑制剂和抗 PD-1 抗体组合对最初不可切除的肝细胞癌的降期和切除

背景：酪氨酸激酶抑制剂 (TKI) 和抗 PD-1 抗体的联合治疗已显示对不可切除的肝细胞癌 (HCC) 患者的高肿瘤缓解率。然而，没有报道使用这种治疗策略将最初不可切除的 HCC 转变为可切除的 HCC。方法：分析了接受 TKI/抗 PD-1 联合抗体一线治疗的连续无法切除的 HCC 患者。使用 RECIST v1.1 每 2 个月（±2 周）通过成像评估肿瘤反应和可切除性。可切除性标准为 (1) R0 切除，具有足够的残肝体积和功能；(2) 肝内病变被评价为部分缓解或病情稳定至少2个月；(3) 未发生严重或持续的不良反应；(4)肝切除术不禁忌。结果：连续招募了 63 名患者。其中，10 例（15.9%）在联合治疗开始后 3.2 个月（范围：2.4-8.3 个月）内接受了 R0 切除。在基线时，这 10 名患者的中位最大肿瘤直径为 9.3 cm，7 名巴塞罗那诊所肝癌 C 期（血管侵犯）疾病，2 名 B 期，1 名 A 期。手术前，6 名患者被评估为部分缓解，3例疾病稳定，1例肝内病变部分缓解，但右侧肾上腺出现新的转移性病变。六名患者（60%）达到病理完全缓解。一名患者在肝切除术后 2.4 个月死于免疫相关的不良反应。在对其他 9 名患者进行 11.2 个月（范围：7.8-15.9 个月）的中位随访后，8 名患者存活且未复发，1 名患者出现肿瘤复发。结论： TKI/抗 PD-1 抗体联合是不可切除 HCC 患者转为可切除的可行转化疗法。该研究代表了关于 TKI 和 PD-1 抗体联合全身治疗对 HCC 的降期作用的最大患者队列。
肝癌