Abou-Alfa Ghassan K, Galle Peter R, Chao Yee, Erinjeri Joseph, Heo Jeong, Borad Mitesh J, Luca Angelo, Burke James, Pelusio Adina, Agathon Delphine, Lusky Monika, Breitbach Caroline, Qin Shukui, Gane Edward
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Weill Medical College, Cornell University, New York, NY, USA.
Liver Cancer. 2023 Sep 30;13(3):248-264. doi: 10.1159/000533650. eCollection 2024 Jun.
Intratumoral administration of pexa-vec (pexastimogene devacirepvec), an oncolytic and immunotherapeutic vaccinia virus, given to patients with hepatocellular carcinoma (HCC), is associated with both local and distant tumor responses. We hypothesized subsequent treatment with sorafenib could demonstrate superior efficacy.
This random phase III open-label study evaluated the sequential treatment with pexa-vec followed by sorafenib compared to sorafenib in patients with advanced HCC and no prior systemic treatment. The primary endpoint is overall survival (OS). Key secondary endpoints included time to progression (TTP), progression-free survival, overall response rate (ORR), and disease control rate (DCR). Safety was assessed in all patients who received ≥1 dose of study treatment.
The study was conducted at 142 sites in 16 countries. From December 30, 2015, to the interim analysis on August 2, 2019, 459 patients were randomly assigned (pexa-vec plus sorafenib: 234, sorafenib: 225). At the interim analysis, the median OS was 12.7 months (95% CI: 9.89, 14.95) in the pexa-vec plus sorafenib arm and 14.0 months (95% CI: 11.01, 18.00) in the sorafenib arm. This led to the early termination of the study. The median TTP was 2.0 months (95% CI: 1.77, 2.96) and 4.2 months (95% CI: 2.92, 4.63); ORR was 19.2% (45 patients) and 20.9% (47 patients); and DCR was 50.0% (117 patients) and 57.3% (129 patients) in the pexa-vec plus sorafenib and sorafenib arms, respectively. Serious adverse events were reported in 117 (53.7%) patients in the pexa-vec plus sorafenib and 77 (35.5%) patients in the sorafenib arm. Liver failure was the most frequently reported in both groups.
Sequential pexa-vec plus sorafenib treatment did not demonstrate increased clinical benefit in advanced HCC and fared worse compared to sorafenib alone. The advent of the added value of checkpoint inhibitors should direct any further development of oncolytic virus therapy strategies.
向肝细胞癌（HCC）患者瘤内注射溶瘤免疫治疗性痘苗病毒pexa-vec（pexastimogene devacirepvec），与局部和远处肿瘤反应均相关。我们假设随后使用索拉非尼治疗可能显示出更高的疗效。
这项随机III期开放标签研究评估了在未接受过全身治疗的晚期HCC患者中，先使用pexa-vec再使用索拉非尼的序贯治疗与单独使用索拉非尼的疗效对比。主要终点是总生存期（OS）。关键次要终点包括疾病进展时间（TTP）、无进展生存期、总缓解率（ORR）和疾病控制率（DCR）。对所有接受≥1剂研究治疗的患者进行安全性评估。
该研究在16个国家的142个地点进行。从2015年12月30日至2019年8月2日的中期分析，459例患者被随机分组（pexa-vec加索拉非尼组：234例，索拉非尼组：225例）。在中期分析时，pexa-vec加索拉非尼组的中位OS为12.7个月（95%CI：9.89，14.95），索拉非尼组为14.0个月（95%CI：11.01，18.00）。这导致研究提前终止。pexa-vec加索拉非尼组和索拉非尼组的中位TTP分别为2.0个月（95%CI：1.77，2.96）和4.2个月（95%CI：2.92，4.63）；ORR分别为19.2%（45例患者）和20.9%（47例患者）；DCR分别为50.0%（117例患者）和57.3%（129例患者）。pexa-vec加索拉非尼组117例（53.7%）患者和索拉非尼组77例（35.5%）患者报告了严重不良事件。两组中最常报告的都是肝衰竭。
序贯使用pexa-vec加索拉非尼治疗在晚期HCC中未显示出临床获益增加，且与单独使用索拉非尼相比效果更差。检查点抑制剂附加值的出现应指导溶瘤病毒治疗策略的任何进一步发展。
