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标题: 罗氏的Tecentriq和Avastin在中国获准用于最常见肝癌患者 [打印本页]

作者: StephenW    时间: 2020-10-31 09:18     标题: 罗氏的Tecentriq和Avastin在中国获准用于最常见肝癌患者

Roche’s Tecentriq in combination with Avastin approved in China for people with the most common form of liver cancer

October 29, 2020 2:00 AM EDT
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    Tecentriq in combination with Avastin is the first and only cancer immunotherapy regimen approved for the treatment of unresectable hepatocellular carcinoma (HCC), the most common form of liver cancer
    The Tecentriq combination improved overall survival and progression-free survival compared with sorafenib in people with unresectable HCC
    Approval by the China National Medical Products Administration brings a new treatment option to HCC patients in China, where almost half of all cases worldwide are found

            
Basel, 29 October 2020 – Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the China National Medical Products Administration (NMPA) has approved Tecentriq® (atezolizumab) in combination with Avastin® (bevacizumab) for the treatment of people with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy.

“Today’s approval of Tecentriq in combination with Avastin for unresectable hepatocellular carcinoma means that people in China now have a cancer immunotherapy option which is changing the treatment landscape for this aggressive disease”, said Levi Garraway, M.D., Ph.D., Roche's Chief Medical Officer and Head of Global Product Development. “With almost half of the world’s hepatocellular carcinoma cases diagnosed in China, this approval marks a major advance for Chinese patients.”

“In China, primary liver cancer ranks as the fourth most common malignancy and is the second leading cause of cancer death. With most patients diagnosed at the intermediate and advanced stages where surgery or other locoregional therapies are not an option, there is an urgent need for effective treatments for unresectable HCC”, said Prof. Shukui Qin, Leading Principal Investigator of the IMbrave150 study in China and Chairman of the Liver Cancer Expert Committee of the Chinese Society of Clinical Oncology (CSCO). “The IMbrave150 study demonstrated that the combination of Tecentriq and Avastin in this setting can significantly improve outcomes for patients. It is truly gratifying news that the combination is now approved in China and gives a new option to Chinese liver cancer patients.”

Liver cancer is one of the most common cancers in China, accounting for nearly 400,000 diagnoses and approximately 368,000 deaths every year, equivalent to over 1,000 per day.1 Only 20% of people with HCC in China are diagnosed in the early stages, when curative treatments are still an option.2 The average 5-year survival rate for people in China with liver cancer is only approximately 15%.3 Roche is committed to tackling liver disease right across the disease journey, from the earliest stages through to advanced disease, with the ultimate goal of one day stopping chronic liver disease.

The approval was based on results of the Phase III IMbrave150 study, which included analyses of a cohort of Chinese patients (n=194) from the same study. Data from this cohort were consistent with the global results. Among Chinese patients, Tecentriq in combination with Avastin reduced the risk of death (overall survival; OS) by 56% (hazard ratio [HR]=0.44; 95% CI: 0.25–0.76) and reduced the risk of disease worsening or death (progression-free survival; PFS) by 40% (HR=0.60; 95% CI: 0.40–0.90), compared with sorafenib. Tecentriq and Avastin were generally well-tolerated with manageable toxicities, and the safety profile was consistent with the known safety profiles of the individual medicines and with the underlying disease.

Global results from the IMbrave150 study demonstrated that Tecentriq in combination with Avastin reduced the risk of death (OS) by 42% (HR=0.58; 95% CI: 0.42–0.79; p=0.0006) and reduced the risk of disease worsening or death (PFS) by 41% (HR=0.59; 95% CI: 0.47–0.76; pNew England Journal of Medicine on 14 May 2020.4

In May 2020, the US Food and Drug Administration approved Tecentriq in combination with Avastin for the treatment of people with unresectable or metastatic HCC who have not received prior systemic therapy. In addition, in September, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended the approval of Tecentriq in combination with Avastin for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy. Tecentriq in combination with Avastin was also recently recommended as a preferred option by the CSCO for the treatment of unresectable HCC, as well as by many clinical practice guidelines globally.

Earlier this year, the China NMPA also approved Tecentriq in combination with chemotherapy (carboplatin and etoposide) for the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC), an area of major unmet need and one that has seen limited advances in treatment until now. The submission was based on the results from the positive Phase III IMpower133 study and was the first cancer immunotherapy available in China for the initial treatment of ES-SCLC.

Roche has an extensive development programme for Tecentriq, including multiple ongoing and planned Phase III studies, across several types of lung, genitourinary, skin, breast, gastrointestinal, gynaecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

About the IMbrave150 study
IMbrave150 is a global Phase III, multicentre, open-label study of 501 people with unresectable HCC who had not received prior systemic therapy. People were randomised 2:1 to receive the combination of Tecentriq and Avastin or sorafenib. Tecentriq was administered intravenously (IV), 1200 mg on day 1 of each 21-day cycle, and Avastin was administered IV, 15 mg/kg on day 1 of each 21-day cycle. Sorafenib was administered by mouth, 400 mg twice per day, on days 1-21 of each 21-day cycle. People received the combination or the control arm treatment until disease progression or unacceptable toxicity. The two primary endpoints were OS and independent review facility (IRF)-assessed PFS per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Additional study endpoints included IRF-assessed overall response rate (ORR) per RECIST v1.1 and HCC mRECIST.

About hepatocellular carcinoma
HCC, the most common form of liver cancer, is an aggressive cancer with limited treatment options and is a major cause of cancer deaths worldwide.5 Every year, more than 750,000 people worldwide are diagnosed with HCC,5,6 with the majority of cases in Asia and almost half of all cases in China.1,6 In the US, the number of liver cancer cases have more than tripled since 1980 and HCC represents the fastest-rising cause of cancer-related death, while in Europe, liver cancer is also on the rise.7-9 HCC develops predominantly in people with cirrhosis due to chronic hepatitis (B or C) or alcohol consumption, and typically presents at an advanced stage.5 The prognosis for unresectable HCC remains poor, with few systemic therapeutic options and a 1-year survival rate of less than 50% following diagnosis.10

About the Tecentriq and Avastin combination
There is a strong scientific rationale to support the use of Tecentriq plus Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq’s ability to restore anti-cancer immunity, by inhibiting vascular endothelial growth factor (VEGF)-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer and in PD-L1-positive metastatic triple-negative breast cancer. In the US, China and a number of other countries, Tecentriq in combination with Avastin is approved for a type of liver cancer.

About Avastin
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called VEGF that plays an important role throughout the lifecycle of the tumour to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumour blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumour blood supply is thought to be critical to a tumour’s ability to grow and spread in the body (metastasise).

作者: StephenW    时间: 2020-10-31 09:21

罗氏的Tecentriq和Avastin在中国获准用于最常见肝癌患者


    Tecentriq联合Avastin是第一种也是唯一一种被批准用于治疗不可切除的肝细胞癌(HCC)(最常见的肝癌形式)的癌症免疫疗法
    与索拉非尼相比,Tecentriq组合改善了无法切除的HCC患者的总体生存率和无进展生存期
    中国国家药品监督管理总局的批准为中国的HCC患者带来了新的治疗选择,全世界几乎有一半的病例被发现

            
2020年10月29日,巴塞尔–罗氏(Rox)(六:RO,ROG; OTCQX:RHHBY)今天宣布,中国国家药品监督管理局(NMPA)已批准将Tecentriq®(atezolizumab)与Avastin®(贝伐单抗)结合使用患有不可切除的肝细胞癌(HCC)且未接受过先前的全身性治疗。

罗氏首席医学博士Levi Garraway博士说:“今天批准Tecentriq与Avastin联合用于不可切除的肝细胞癌,意味着中国人现在可以选择癌症免疫疗法,这正在改变这种侵袭性疾病的治疗方式。”全球产品开发官兼主管。 “在中国诊断出世界上近一半的肝细胞癌病例后,这一批准标志着中国患者的重大进步。”

“在中国,原发性肝癌是第四大最常见的恶性肿瘤,是癌症死亡的第二大主要原因。 IMbrave150研究的主要负责人秦淑奎教授说:“由于大多数患者被诊断为不能选择手术或其他局部治疗的中晚期,因此迫切需要对无法切除的肝癌进行有效治疗。”中国临床肿瘤学会(CSCO)肝癌专家委员会主席:“ IMbrave150研究表明,在这种情况下将Tecentriq和Avastin结合使用可显着改善患者的预后。令人欣喜的消息是,该组合现已在中国获得批准,为中国肝癌患者提供了新的选择。”

肝癌是中国最常见的癌症之一,每年诊断近40万例癌症,约368,000例死亡,相当于每天超过1,000例。 1在中国,只有20%的HCC患者在早期仍被诊断出,而仍然可以选择治疗。 2中国肝癌患者的平均5年生存率仅约15%。 3罗氏(Roche)致力于从早期阶段到晚期疾病的整个疾病发展过程中应对肝病,最终目标是一天停止慢性肝病。

该批准是基于III期IMbrave150研究的结果,该研究包括对同一研究中一组中国患者(n = 194)的分析。该队列的数据与总体结果一致。在中国患者中,Tecentriq与Avastin联合使用可将死亡风险(总体生存; OS)降低56%(风险比[HR] = 0.44; 95%CI:0.25-0.76),并降低疾病恶化或死亡的风险(与索拉非尼相比,无进展生存期(PFS)提高了40%(HR = 0.60; 95%CI:0.40-0.90)。 Tecentriq和Avastin通常具有良好的耐受性,且毒性易于控制,其安全性与个体药物的已知安全性及潜在疾病一致。

IMbrave150研究的全球结果表明,Tecentriq与Avastin结合可使死亡风险(OS)降低42%(HR = 0.58; 95%CI:0.42-0.79; p = 0.0006),并降低疾病恶化或死亡的风险(PFS)上升41%(HR = 0.59; 95%CI:0.47-0.76; pNew England Journal of Medicine于2020.4年5月14日发布)
2020年5月,美国食品和药物管理局批准了Tecentriq与Avastin的组合,用于治疗无法切除或转移性HCC且未接受过先前全身治疗的患者。此外,9月,欧洲药品管理局(EMA)人用药用产品委员会(CHMP)建议批准Tecentriq与Avastin联合用于治疗尚未接受治疗的晚期或不可切除肝细胞癌(HCC)的成年患者接受过先前的全身治疗。最近,CSCO还推荐Tecentriq与Avastin结合作为治疗无法切除的HCC的首选方案,并且被全球许多临床实践指南推荐为首选方案。

今年早些时候,中国NMPA还批准了Tecentriq联合化学疗法(卡铂和依托泊苷)用于一线治疗患有广泛期小细胞肺癌(ES-SCLC)的患者,该领域是主要未满足需求的领域,到目前为止,治疗进展有限。该报告基于IMpower133 III期研究的阳性结果,是中国首例可用于ES-SCLC初始治疗的癌症免疫疗法。

罗氏(Roche)为Tecentriq制定了广泛的开发计划,包括多项正在进行的和计划中的III期研究,涉及多种类型的肺癌,泌尿生殖道癌,皮肤癌,乳腺癌,胃肠道癌,妇科癌和头颈癌。这包括单独或与其他药物联合评估Tecentriq的研究。

关于IMbrave150研究
IMbrave150是一项全球性的,多中心,开放性的III期研究,研究对象是501例无法手术的HCC患者,他们之前没有接受过全身治疗。人们按照2:1的比例随机接受Tecentriq和Avastin或sorafenib的组合。在每个21天周期的第1天静脉注射(IV)1200 mg的Tecentriq,在每个21天周期的第1天静脉注射15 mg / kg的Avastin。在每个21天周期的第1-21天,每天口服两次400 mg索拉非尼。人们接受联合治疗或对照组治疗直至疾病进展或出现不可接受的毒性。两个主要终点是根据实体肿瘤版本1.1(RECIST v1.1)中的反应评估标准,由OS和独立审查工具(IRF)评估的PFS。其他研究终点包括根据RECIST v1.1和HCC mRECIST进行IRF评估的总体缓解率(ORR)。

关于肝细胞癌
肝癌(HCC)是最常见的肝癌形式,是一种侵袭性癌症,治疗选择有限,并且是全世界癌症死亡的主要原因。5每年,全世界有超过750,000人被诊断出患有HCC [5,6]在亚洲,几乎是中国所有病例的一半。1,6在美国,自1980年以来,肝癌病例的数量增加了两倍多,HCC是癌症相关死亡上升最快的原因,而在欧洲,肝癌肝癌的发生也呈上升趋势。7-9肝癌主要由慢性乙型或丙型肝炎或饮酒引起的肝硬化患者发展,并且典型地处于晚期。5无法切除的肝癌的预后仍然很差,几乎没有全身性治疗诊断后的1年生存率低于50%10。

关于Tecentriq和Avastin组合
有强有力的科学依据来支持将Tecentriq和Avastin结合使用。 Tecentriq和Avastin疗法可能会增强免疫系统对抗多种癌症的潜力。阿瓦斯汀除了具有公认的抗血管生成作用外,还可以通过抑制血管内皮生长因子(VEGF)相关的免疫抑制作用,促进T细胞肿瘤浸润并实现T的激活和活化,进一步增强Tecentriq恢复抗癌免疫力的能力。 -细胞对肿瘤抗原的反应。

关于Tecentriq
Tecentriq是一种单克隆抗体,旨在与称为PD-L1的蛋白质结合,该蛋白质在肿瘤细胞和肿瘤浸润免疫细胞上表达,从而阻断其与PD-1和B7.1受体的相互作用。通过抑制PD-L1,Tecentriq可以激活T细胞。 Tecentriq是一种癌症免疫疗法,有潜力与其他免疫疗法,靶向药物和多种化学疗法在多种癌症中作为基础联合治疗伙伴。 Tecentriq及其临床程序的开发是基于我们对免疫系统如何与肿瘤相互作用以及如何利用人的免疫系统更有效地抗击癌症的理解。
Tecentriq已在美国,欧盟和世界各地的国家中单独或与各种非小细胞和小细胞肺癌,某些类型的转移性尿路上皮癌以及PD-中的靶向疗法和/或化学疗法结合使用获批L1阳性转移性三阴性乳腺癌。在美国,中国和其他许多国家,Tecentriq与Avastin的组合被批准用于某种肝癌。

关于阿瓦斯汀
阿瓦斯汀是仅用于处方的药物,是静脉输液的解决方案。它是一种生物抗体,旨在与称为VEGF的蛋白质特异性结合,该蛋白质在肿瘤的整个生命周期中起着重要作用,以发育和维持血管,这一过程称为血管生成。 Avastin设计为通过直接结合VEGF蛋白来阻止与血管细胞受体的相互作用,从而干扰肿瘤的血液供应。人们认为,肿瘤的血液供应对肿瘤在体内生长和扩散的能力至关重要(转移)。




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