Introduction: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. When tumor shrinkage is obtained, achieving complete response (CR) is possible in many cases using curative conversion with resection, ablation, or super selective transarterial chemoembolization (TACE) with curative intent. This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter proof-of-concept study was conducted to show the value of curative conversion in immunotherapy-treated intermediate-stage HCC meeting TACE-unsuitable criteria. Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. CR rate, drug-free rate, time to CR, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, progression-free survival (PFS), and overall survival (OS) were assessed in patients who achieved CR using resection, ablation, super selective TACE with curative intent following atezolizumab plus bevacizumab or atezolizumab plus bevacizumab alone. Results: Clinical or pathological CR was achieved in 38 patients (35%) (median observation period: 21.2 months). The modalities of curative conversion in 35 patients were as follows: resection, 7; ablation, 13; and superselective TACE, 15. Three patients achieved clinical CR with atezolizumab plus bevacizumab therapy alone. Among the 38 CR patients, 25 achieved drug-free status. PFS was not reached, and three patients experienced recurrence after reaching CR. Regarding OS, there were no deaths in any of the CR patients. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved CR with atezolizumab plus bevacizumab followed by curative conversion, five achieved drug-free status. Discussion/Conclusion: The achievement of CR rate by curative conversion in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 23% of patients achieved drug-free status and no recurrence was observed from this patient subgroup with CR and drug free status. Thus, achieving CR and/or drug-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread.


中文翻译：

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Atezolizumab 加贝伐单抗联合或不联合治疗不适合经动脉化疗栓塞的中期肝细胞癌患者实现完全缓解和无药状态：一项多中心概念验证研究

简介：据 IMbrave150 试验报告，Atezolizumab 联合贝伐珠单抗疗法在治疗中期肝细胞癌 (HCC) 方面极为有效，有效率达 44%。当肿瘤缩小时，在许多情况下，通过切除、消融或超选择性经动脉化疗栓塞 (TACE) 进行治愈性转化，有可能实现完全缓解 (CR)。这一概念，即全身治疗和局部治疗相结合的治愈性转化，以前从未有过报道。这项多中心概念验证研究的目的是展示免疫疗法治疗的符合 TACE 不合适标准的中期 HCC 的治愈性转化的价值。方法：本研究纳入了 110 名连续的 Child-Pugh A 级患者，他们在日本的 7 个中心接受了 atezolizumab 加贝伐单抗作为一线治疗，治疗不可切除且不适合 TACE 的中期 HCC。对达到 CR 的患者评估 CR 率、无药率、达到 CR 的时间、肝功能变化、正电子发射断层扫描 (PET) 阳性 HCC 的疗效、无进展生存期 (PFS) 和总生存期 (OS)在 atezolizumab 加贝伐单抗或单独使用 atezolizumab 加贝伐单抗后，使用切除、消融、超选择性 TACE 进行治疗。结果：38 名患者（35%）达到临床或病理 CR（中位观察期：21.2 个月）。35例患者的治愈性转化方式如下：切除7例；消融，13；和超选择性 TACE，15。三名患者仅通过阿特珠单抗加贝伐单抗治疗达到了临床 CR。在38名CR患者中，25名达到了无药物状态。未达到 PFS，3 名患者在达到 CR 后出现复发。关于 OS，没有任何 CR 患者死亡。局部治疗或切除后，白蛋白-胆红素评分并未恶化。在 7 名 PET 阳性患者中，使用阿替利珠单抗加贝伐单抗实现 CR，随后实现治愈性转化，其中 5 名患者达到了无药物状态。讨论/结论：对于不可切除且不适合 TACE 的中期 HCC，采用阿替珠单抗加贝伐单抗作为前期治疗的患者通过治愈性转化实现 CR 率为 35%。总体而言，23% 的患者达到了无药物状态，并且在这个具有 CR 和无药物状态的患者亚组中没有观察到复发。因此，对于没有血管侵犯或肝外扩散的中期 HCC 患者来说，实现 CR 和/或无药物状态应该是治疗目标。