ESMO 2024丨研究者说:HIMALAYA研究5年OS更新,晚期肝癌一线治疗生存再创新高

健康   2024-10-05 15:21   山西  




编者按:晚期肝癌的免疫治疗进展迅速,已成为标准的一线治疗手段。2024年欧洲肿瘤内科学会(ESMO)大会(9月13~17日,巴塞罗那)上展示的一项HIMALAYA研究评估了新型免疫治疗组合STRIDE—tremelimumab和度伐利尤单抗与索拉非尼的比较。主要研究者、意大利胡曼尼塔斯大学的Lorenza Rimassa教授在现场接受了我们的专访。



研究概况

947MO - Five-year overall survival (OS) and OS by tumour response measures from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma (uHCC)
tremelimumab联合度伐利尤单抗治疗不可切除肝细胞癌的III期HIMALAYA研究的五年总生存期和肿瘤反应评估的OS


背景


在uHCC的Ⅲ期HIMALAYA研究(NCT03298451)中,STRIDE(tremelimumab联合度伐利尤单抗)在初步分析中与索拉非尼相比显著改善了患者的OS,并显示出持久的长期生存率,4年OS率为25.2%。在这里,我们报告了uHCC的第一个5年OS分析,并通过多种肿瘤缓解指标评估患者的生存率。

方法


患有uHCC的参与者被随机分配到STRIDE、度伐利尤单抗单药治疗或索拉非尼组。研究者发表对OS、5年OS率、疾病控制(DC)的OS、肿瘤大小和反应深度以及严重不良事件(SAE)进行了评估(图1)。数据截止日期为2024年3月1日。


图1. 研究设计

结果


STRIDE与索拉非尼的OS风险比(HR)为0.76(95%CI:0.65~0.89)。STRIDE组的5年OS率为19.6%,索拉非尼组为9.4%(HR :2.09),且在达到DC的患者中进一步改善(28.7% vs. 12.7%;HR :2.26)(图2)。STRIDE与索拉非尼组达到≥G2(>25%)肿瘤缩小的患者48个月的OS率分别为58.0% vs. 36.0%;60个月的OS率分别为50.7% vs. 26.3%(图3)。STRIDE治疗相关SAE的发生率与主要分析相比没有变化。

图2.STRIDE与索拉非尼的5年OS率

图3.两组间根据缓解深度和肿瘤缩小程度评估的OS


结论


STRIDE显示出前所未有的5年生存率,在延长的随访中没有额外的严重安全事件。在包括DC和DpR在内的多种肿瘤反应评估中观察到的OS结局改善,为双重免疫检查点抑制的临床获益提供了新的观点,超越了传统的反应评估手段。这些结果为uHCC树立了新的标杆,STRIDE方案每5例患者中就有1例患者在5年时存活。



研究者说

肿瘤瞭望消化时讯:恭喜您的壁报被选为本次ESMO会议的口头报告。您能向我们介绍一下您研究的背景和主要结果吗?



Rimassa 医生:本项研究是基于HIMALAYA研究的最新总生存期分析。HIMALAYA研究是一项针对不可切除HCC患者的Ⅲ期研究,旨在评估STRIDE方案的新免疫治疗组合(即先给予一剂tremelimumab进行预处理,随后使用度伐利尤单抗)与索拉非尼的疗效。该研究还设立了一个度伐利尤单抗单药组,以测试其相对于索拉非尼的非劣效性。该试验已获得阳性结果并已发表,且STRIDE方案已在多个国家/地区进入临床实践。今天展示的数据是五年的总生存率分析。在此分析中,我们发现19.7%的患者在五年后仍然存活,而索拉非尼组这一比例仅为9.4%。HIMALAYA是首个且唯一一项在晚期HCC中报告了五年总生存率数据的Ⅲ期试验。这些数据前所未有:五年后仍有五分之一的患者存活——这是我们在不可切除HCC患者中从未见过的情况。本项分析的另一个重要发现是,实现长期生存并不一定需要达到客观缓解,因此病情稳定的患者也可能实现长期生存。如果我们考虑疾病控制(DC)的患者,那么五年后存活的患者比例为28.7%。另一个重要的点是,安全性特征随着时间的推移而未发生变化,且在此分析中未观察到新的严重治疗相关不良事件。


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Dr Rimassa: Thank you for the question. This study is the updated overall survival analysis from the HIMALAYA study. The HIMALAYA study is a phase III study in patients with unresectable HCC testing a new immunotherapy combination called STRIDE - a single priming dose of tremelimumab followed by durvalumab - versus sorafenib. The trial also included a durvalumab single agent arm tested for non-inferiority versus sorafenib. The trial is positive and already published, and the STRIDE regimen is already in clinical practice in several countries. The data presented today are the five-year overall survival analysis. In this analysis, we showed that 19.7% of the patients are alive at five years, versus 9.4% in the sorafenib arm. HIMALAYA is the first and only phase III trial in advanced HCC with overall survival data at five years. These data are unprecedented with one-in-five patients alive at five years - something that we have not seen before in patients with unresectable HCC. The other important point of this analysis is that an objective response is not needed to achieve long-term survival, so patients with stable disease may also achieve long-term survival. If we consider patients with disease control (DC), 28.7% of them are alive at five years. Another important point is that the safety profile did not change over time, and no new serious treatment-related adverse events were observed in this analysis.


肿瘤瞭望消化时讯:您认为对晚期肝癌患者的临床意义是什么?



Rimassa 医生:这些数据对于临床实践而言至关重要。我们正与同事们就此进行深入探讨,因为这是首次有Ⅲ期临床试验报告了五年的总生存率。以往,不可切除肝细胞癌(HCC)患者的五年总生存率低于5%,而使用酪氨酸激酶抑制剂的患者其生存率也不足10%。如今,我们已有近20%的患者存活至五年,因此,在为患者选择一线治疗方案时,这一点是我们在临床实践中必须考虑的重要因素。


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Dr Rimassa: These data are really important for clinical practice. We are discussing it with our colleagues, because it is the first time that a phase III trial has reported five-year overall survival. Historically, five-year overall survival of patients with unresectable HCC was <5%, and with the tyrosine kinase inhibitors <10%. Now we have almost 20% of patients have survived to five years, so this is an important point we have to consider in clinical practice when we select our first-line treatment for our patients.


肿瘤瞭望消化时讯:肝癌免疫治疗的临床进展如何?



Rimassa 医生:近年来,我们进行了一些Ⅲ期临床试验,它们揭示了不同免疫治疗组合或单药免疫治疗对晚期或不可切除HCC患者的益处。目前,有两种组合已在多个国家进入临床实践:一种是阿替利珠单抗联合贝伐珠单抗,另一种则是根据STRIDE方案使用的度伐利尤单抗联合tremelimumab。此外,还有一种组合——卡瑞利珠单抗联合rivoceranib(注:国内上市名称为阿帕替尼,商品名:艾坦),已在中国获批,但在其他国家尚未获得批准。关于伊匹单抗联合纳武利尤单抗的数据也呈阳性,这些数据已在ASCO及今年的ESMO 2024大会上展示,不过该组合目前尚未获批,也尚未进入临床实践。一些单药治疗方案,如阿替利珠单抗或度伐利尤单抗单药治疗,已在一些国家被批准作为不可切除HCC患者的一线治疗方案。因此,我们在一线治疗方面拥有多种选择。目前,一些试验正在测试其他免疫治疗组合——包括双重免疫治疗和三重免疫治疗组合——在一线治疗中的应用。我们需要确定每位患者的最佳治疗方案及最佳治疗顺序,因为在后续治疗线上我们尚无可靠的数据。但对于不可切除HCC患者而言,近年来随着免疫治疗组合成为一线治疗的标准方案,其治疗选择已发生了彻底改变。


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Dr Rimassa: In recent years, we have had some phase III trials showing the benefits of different immunotherapy combinations or immunotherapy as a single agent for patients with advanced or unresectable HCC. We have two combinations that are already in clinical practice in several countries - atezolizumab plus bevacizumab, and durvalumab and tremelimumab according to the STRIDE regimen. We also have another combination, camrelizumab plus rivoceranib, now approved in China, but not yet approved in other countries. And we have data for ipilimumab plus nivolumab that are positive as well that were presented at ASCO and here at ESMO 2024, but this combination is not yet approved and not yet in clinical practice. I will also mention some single agents, like atezolizumab or durvalumab single agents, that are approved in some countries for patients with unresectable HCC in the first-line. So we have different options in first-line. There are ongoing trials testing other immunotherapy combinations - dual immunotherapy as well as triple immunotherapy combinations - in first-line. We need to identify which is the best treatment for every patient, and what is the best sequence, because we don’t have solid data in the following lines. But for patients with unresectable HCC, the treatment options have changed completely in recent years with immunotherapy combinations as first-line standard-of-care.



来源:肿瘤瞭望消化时讯




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《肿瘤瞭望》于2014年初创刊,由著名肿瘤科专家徐兵河院士担任总编辑,以“同步传真国际肿瘤进展”为办刊宗旨,以循证医学理念为指导思想,采用全媒体组合报道模式,致力于为国内广大肿瘤临床、教研人员搭建一座与国际接轨的桥梁。
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