一线组合可提高晚期肝癌的生存率 与索拉非尼相比，总生存

StephenW

First-Line Combo Improves Survival in Advanced HCC
Decreases in overall survival, progression-free survival hazards by almost 50% compared with sorafenib


    by Charles Bankhead, Senior Editor, MedPage Today
    November 22, 2019

For the first time in more than a decade, patients with hepatocellular carcinoma (HCC) lived significantly longer with a new upfront therapy than with an existing standard of care.

The PD-L1 inhibitor atezolizumab (Tecentriq) plus the angiogenesis inhibitor bevacizumab (Avastin) reduced the survival hazard by 42% and the risk of disease progression by 41% as compared with the targeted VEGF inhibitor sorafenib (Nexavar) alone.

The median overall survival (OS) had yet to be reached in the combination arm as compared with a median OS of 13.2 months with sorafenib. Median progression-free survival was 6.8 months with the combination versus 4.3 months with sorafenib, as reported at the European Society for Medical Oncology Asia Congress in Singapore.

"This is the first study in 11 years to show an improvement in survival with a new first-line treatment option compared to sorafenib, which has been the standard of care throughout this time," Ann-Lii Cheng, MD, of the National Taiwan University Cancer Center in Taipei, said in a statement. "Atezolizumab plus bevacizumab has the potential to be a practice-changing treatment option in hepatocellular carcinoma."

British oncologist Angela Lamarca, MD, PhD, of the Christie NHS Foundation Trust in Manchester, England, agreed with Cheng's assessment: "I think this is a breakthrough, and based on the results, the combination of atezolizumab could become the new standard of care," she said.

Ian Chau, MD, of the Royal Marsden Hospital in London, called the results "very encouraging," but noted that "with the high cost of immunotherapy and antiangiogenic agents, it will also be important that those drugs are accessible to patients."

Cheng reported the primary results of the phase III, randomized IMbrave150 trial, which involved 501 patients with unresectable HCC. Investigators in Asia, Europe, and North America randomized patients 2:1 to the combination or to single-agent sorafenib. The trial had co-primary endpoints of OS and PFS.

After a median follow-up of 8.6 months, patients in the atezolizumab-bevacizumab arm had a survival hazard ratio (HR) of 0.58 (P=0.0006) versus the sorafenib group and a PFS HR of 0.59 (P<0.0001). The combination produced objective responses in 27% of patients versus 12% with sorafenib by independent review (P<0.0001) and in 33% vs 13% by independent review of HCC-specific response criteria. Results were generally consistent across all prespecified subgroups, Cheng reported.

Rates of grade 3/4 adverse events were similar with the combination (57%) and sorafenib (55%), as were the rates of fatal adverse events (5% vs 6%). Atezolizumab plus bevacizumab also delayed deterioration in patient-reported quality of life as compared with sorafenib.

The study was funded by F. Hoffmann-La Roche.

Cheng disclosed relationships with Roche/Genentech, Bayer Schering Pharma, Bristol-Myers Squibb, Eisai, Merck Serono, Novartis, Ono Pharmaceutical, Exelixis, Nucleix, IQVIA, Bayer Yakuhin, Amgen Taiwan, and Merck Sharp & Dohme.

    Primary Source
    ESMO Asia Congress
    Source Reference: Cheng AL, et al "IMbrave150: Efficacy and safety results from a ph III study evaluating atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (Sor) as first treatment (tx) for patients (pts) with unresectable hepatocellular carcinoma (HCC)" ESMO Asia 2019; Abstract LBA3.

StephenW

一线组合可提高晚期肝癌的生存率
与索拉非尼相比，总生存率降低，无进展生存风险降低近50％


今日MedPage高级编辑Charles Bankhead
十一月22，2019

十多年来，使用新的前期治疗方法使肝细胞癌（HCC）患者的寿命明显长于现有的标准治疗方法。

与单独的靶向VEGF抑制剂索拉非尼（Nexavar）相比，PD-L1抑制剂atezolizumab（Tecentriq）加上血管生成抑制剂贝伐单抗（Avastin）降低了42％的生存危险和41％的疾病进展风险。

与索拉非尼组相比，中位总生存期（OS）尚未达到中位总生存期（OS），而索拉非尼的中位生存期为13.2个月。在新加坡举行的亚洲欧洲医学肿瘤学会大会上报道，联合使用的中位无进展生存期为6.8个月，而索拉非尼为4.3个月。

“这是11年以来的第一项研究，显示与索拉非尼相比，采用新的一线治疗方案可以提高生存率，索拉非尼一直以来都是这种治疗的标准，”台湾国家医学研究所的郑安丽医师台北大学癌症中心在一份声明中说。 “ Atezolizumab加贝伐单抗有可能成为改变肝细胞癌治疗方法的一种选择。”

英国曼彻斯特克里斯蒂NHS基金会信托基金的英国肿瘤学家Angela Lamarca医师同意Cheng的评估：“我认为这是一个突破，基于结果，阿特珠单抗的联合治疗可能成为新的治疗标准，“ 她说。

伦敦皇家马斯登医院的医学博士Ian Chau称该结果“非常令人鼓舞”，但他指出“由于免疫疗法和抗血管生成剂的高成本，使患者容易获得这些药物也很重要。”

亚洲，欧洲和北美洲的研究人员将患者按2：1的比例随机分配至联合用药或单药索拉非尼。该试验具有OS和PFS的共同主要终点。

中位随访8.6个月后，与索拉非尼组相比，atezolizumab-bevacizumab组患者的生存危险比（HR）为0.58（P = 0.0006），PFS HR为0.59（P <0.0001）。通过独立评估（P <0.0001），该组合产生了27％的患者客观反应，而索拉非尼则为12％（P <0.0001），独立评估了HCC特异性反应标准的患者为33％vs 13％。程报告说，所有预先指定的亚组的结果总体上是一致的。

3/4级不良事件发生率与联合用药（57％）和索拉非尼（55％）相似，致命不良事件发生率（5％对6％）也是如此。与索拉非尼相比，Atezolizumab加贝伐珠单抗还延迟了患者报告的生活质量恶化。

该研究由F. Hoffmann-La Roche资助。

Cheng透露了与罗氏/基因技术公司，拜耳先灵药业，百时美施贵宝，卫材，默克雪兰诺，诺华，小野制药，Exelixis，Nucleix，IQVIA，拜耳雅库欣，台湾安进和默沙东的关系。

主要资源
ESMO亚洲大会
来源参考：Cheng AL等人，“ IMbrave150：ph III研究评估Atezolizumab（atezo）+ bevacizumab（bev）vs sorafenib（Sor）作为无法切除的肝细胞癌患者（pts）的首次治疗（tx）的疗效和安全性结果（HCC）“ ESMO Asia 2019；摘要LBA3。