Patients with unresectable hepatocellular carcinoma (HCC) treated with the addition of durvalumab and bevacizumab to the standard of care with transarterial chemoembolization (TACE) showed significant improvement in progression-free survival (PFS) in comparison with those treated with TACE alone according to results of the phase 3 EMERALD-1 trial, which was presented at the 2024 ASCO Gastrointestinal Cancers Symposium.¹

The study also found the safety of the combined treatment manageable, with adverse events consistent with the safety profiles of each systemic agent and TACE and low rates of grade 3 and 4 adverse events.

The lead author of the study, Riccardo Lencioni, MD, professor and director of the Cancer Imaging Program in the Department of Diagnostic and Interventional Radiology at Pisa University Hospital in Italy, said in a press release that the results “have the potential to reshape the treatment of this complex disease with a poor prognosis by showing for the first time that adding an immunotherapy combination to TACE significantly improves progression-free survival.”²

Kenneth Tanabe, MD, a surgical oncologist and chief of the Division of Gastrointestinal and Oncologic Surgery at Massachusetts General Hospital, thinks that the evidence is still premature for changing standard practice but says that the results “provide an additional signal that bevacizumab with immunotherapy has activity in HCC.”

“These data should be integrated into discussions with patients when providing treatment recommendations,” he says.

The trial included 616 patients with unresectable HCC without extrahepatic disease who were randomized 1:1:1 to (1) durvalumab, bevacizumab, and TACE; (2) durvalumab and TACE; or (3) TACE alone. The primary outcome of the study, PFS with durvalumab, bevacizumab, and TACE versus TACE alone, showed median PFS values of 15 and 8.2 months, respectively; this represented a 23% reduction in the risk of disease progression or death for the combination regimen (hazard ratio, 0.77; 95% CI, 0.61–0.98; p = .032). No significant differences were seen in secondary outcomes, including PFS for durvalumab and TACE versus TACE alone, overall survival, objective response rates, time to disease progression, and safety.

Dr Tanabe calls the positive results of the trial a “rarity” in this disease, but he cautions that many experts have concern over using PFS as a surrogate end point for overall survival when used in patients with intermediate HCC as opposed to advanced HCC. He notes that the hazard reduction in PFS for patients randomized to durvalumab, bevacizumab, and TACE was only 0.77, a smaller than hoped for improvement in PFS. “Might this be a harbinger of a future report on the final analysis of ‘no difference’ in overall survival?” He adds that a more mature final analysis of this ongoing trial will provide an answer. Also unclear is how the survival of patients treated with durvalumab, bevacizumab, and TACE would compare with the survival of patients treated initially with TACE only, and then with durvalumab and bevacizumab at the time of progression, says Dr Tanabe.

根据以下研究结果，与单独接受 TACE 治疗的患者相比，在经动脉化疗栓塞 (TACE) 护理标准中添加杜瓦鲁单抗 (durvalumab) 和贝伐单抗 (bevacizumab) 治疗的不可切除性肝细胞癌 (HCC) 患者的无进展生存期 (PFS) 显着改善3 期 EMERALD-1 试验，在 2024 年 ASCO 胃肠癌研讨会上提出。¹

研究还发现联合治疗的安全性可控，不良事件与每种全身药物和 TACE 的安全性一致，且 3 级和 4 级不良事件发生率较低。

该研究的主要作者、意大利比萨大学医院诊断和介入放射学系癌症成像项目教授兼主任 Riccardo Lencioni 医学博士在一份新闻稿中表示，研究结果“有可能重塑通过首次证明在 TACE 中添加免疫疗法组合可以显着提高无进展生存期，来治疗这种预后不良的复杂疾病。” ²

麻省总医院胃肠道和肿瘤外科主任兼肿瘤外科医师 Kenneth Tanabe 医学博士认为，改变标准实践的证据还为时过早，但他表示，结果“提供了额外的信号，表明贝伐单抗联合免疫疗法具有活性”在肝癌中。”

“在提供治疗建议时，应将这些数据纳入与患者的讨论中，”他说。

该试验纳入了 616 名无肝外疾病且不可切除的 HCC 患者，他们按照 1:1:1 的比例随机分配至 (1) 德瓦鲁单抗 (durvalumab)、贝伐珠单抗 (bevacizumab) 和 TACE； (2) 杜瓦鲁单抗和 TACE；或 (3) 单独 TACE。该研究的主要结果是，使用 durvalumab、贝伐珠单抗和 TACE 与单独使用 TACE 的 PFS 相比，中位 PFS 值分别为 15 个月和 8.2 个月；这表明联合治疗方案的疾病进展或死亡风险降低了 23%（风险比，0.77；95% CI，0.61–0.98；p = .032）。次要结局没有显着差异，包括 durvalumab 联合 TACE 与单独 TACE 的 PFS、总生存期、客观缓解率、疾病进展时间和安全性。

Tanabe 博士称该试验的积极结果在这种疾病中“罕见”，但他警告说，当用于中度 HCC 患者而不是晚期 HCC 患者时，许多专家对使用 PFS 作为总生存期的替代终点表示担忧。他指出，随机接受 durvalumab、贝伐珠单抗和 TACE 治疗的患者的 PFS 风险降低仅为 0.77，小于 PFS 改善的预期。 “这可能是未来关于总体生存率‘无差异’的最终分析报告的先兆吗？”他补充说，对这项正在进行的试验进行更成熟的最终分析将提供答案。 Tanabe 博士表示，还不清楚的是，使用 durvalumab、贝伐单抗和 TACE 治疗的患者的生存率与最初仅接受 TACE，然后在疾病进展时接受 durvalumab 和贝伐单抗治疗的患者的生存率相比如何。