FDA批准Tecentriq Plus Avastin治疗肝癌

StephenW

FDA Approves Tecentriq Plus Avastin for Liver Cancer

The immunotherapy and targeted therapy combo improved both overall survival and patient-reported outcomes.

July 20, 2020 • By Liz Highleyman

    Share
    Comments
    Print

The Food and Drug Administration has approved a regimen combining the immune checkpoint inhibitor Tecentriq (atezolizumab) and the targeted therapy Avastin (bevacizumab) for the treatment of people with inoperable or metastatic hepatocellular carcinoma, the most common type of liver cancer.

In the Phase III IMbrave150 study, Tecentriq plus Avastin reduced the risk of disease progression or death by 41%, prolonged overall survival and improved quality of life compared with standard-of-care treatment.

Over years or decades, chronic hepatitis B or C, heavy alcohol use, fatty liver disease and other causes can lead to the development of liver cirrhosis and HCC. Liver cancer is often detected late and is difficult to treat, making it one of the leading causes of cancer-related death.

The IMbrave150 trial (ClinicalTrials.gov number NCT03434379) included 501 people with inoperable locally advanced or metastatic liver cancer who had not yet received systemic treatment. They were randomly assigned to receive Tecentriq plus Avastin, both administered by IV infusion every three weeks, or twice-daily oral Nexavar (sorafenib) until they experienced disease progression or unacceptable side effects.

Tecentriq is a PD-L1 checkpoint inhibitor that restores T-cell activity against cancer. Avastin is a monoclonal antibody that blocks VEGF, a protein that promotes the proliferation of blood vessels that supply tumors and plays a role in immune suppression. Nexavar is a multikinase inhibitor that blocks the action of several enzymes, including VEGFR, BRAF and RET, involved in cell growth pathways.

Primary results from the study were presented at the European Society for Medical Oncology Asia Congress last November, showing that Tecentriq plus Avastin reduced the risk of disease progression or death by 41% (median 6.8 versus 4.3 months). Overall survival was 13.2 months in the Nexavar group but was not reached in the combination therapy group because most patients were still alive. Overall response rates, meaning complete or partial tumor shrinkage, were 28% versus 12%, respectively.

At the American Society of Clinical Oncology Gastrointestinal Cancers Symposium in January, researchers reported that Tecentriq plus Avastin led to improved quality of life and delayed worsening of symptoms.

Tecentriq plus Avastin recipients reported about a 30% decline in their quality of life, compared with about a 40% decline among Nexavar recipients. A similar pattern was seen for physical functioning and role functioning. For all three measures, the time to deterioration was substantially longer for those taking the combination regimen. Those using Tecentriq plus Avastin also reported a longer period before they experienced worsening of symptoms including loss of appetite, diarrhea, fatigue and pain.

The most common adverse reactions among people taking Tecentriq plus Avastin group are hypertension, fatigue and protein in the urine. IMbrave150 participants who used Tecentriq plus Avastin were more likely to experience fever, abnormal liver and kidney biomarkers and infusion reactions, while those taking Nexavar had more diarrhea and hand-foot syndrome (redness, swelling and pain on the palms of the hands and soles of the feet).

The recommended dose of Tecentriq is 1,200 milligrams mg, followed by 15 mg per kilogram of Avastin administered on the same day every three weeks. If Avastin is discontinued, Tecentriq should be given either as 840 mg every two weeks, 1,200 mg every three weeks or 1,680 mg every four weeks.

“The results of the IMbrave150 study are really transformative for patients with advanced liver cancer, one of the few cancers with a rising death rate and limited options in the first-line setting,” Richard Finn, MD, of the David Geffen School of Medicine and the UCLA Jonsson Comprehensive Cancer Center said in a Genentech press release. “For the first time we have a regimen that markedly improves survival over sorafenib, the standard of care for first-line hepatocellular carcinoma since 2007, and offers patients the opportunity for improved disease control with a favorable tolerability profile.”

StephenW

FDA批准Tecentriq Plus Avastin治疗肝癌

免疫疗法和靶向疗法的组合可改善总体生存率和患者报告的结局。

2020年7月20日•丽兹·海莉曼（Liz Highleyman）

    分享
    注释
    打印

美国食品药物管理局已经批准了一种结合免疫检查点抑制剂Tecentriq（atezolizumab）和靶向疗法Avastin（bevacizumab）的方案，用于治疗无法手术或转移性肝细胞癌（最常见的肝癌类型）。

在III期IMbrave150研究中，与标准治疗相比，Tecentriq加Avastin将疾病进展或死亡的风险降低了41％，延长了总生存期并改善了生活质量。

数年或数十年以来，慢性乙型或丙型肝炎，大量饮酒，脂肪肝疾病和其他原因可导致肝硬化和肝癌的发展。肝癌通常被发现较晚并且难以治疗，使其成为癌症相关死亡的主要原因之一。

IMbrave150试验（ClinicalTrials.gov编号NCT03434379）包括501例尚未接受全身治疗的局部无法手术的局部晚期或转移性肝癌患者。他们被随机分配接受Tecentriq加Avastin，每三周一次静脉输注，或每天两次口服Nexavar（索拉非尼），直到他们经历疾病进展或不可接受的副作用。

Tecentriq是一种PD-L1检查点抑制剂，可恢复针对癌症的T细胞活性。阿瓦斯汀是一种单克隆抗体，可阻断VEGF，该蛋白可促进供应肿瘤的血管增殖并在免疫抑制中起作用。 Nexavar是一种多激酶抑制剂，可阻断细胞生长途径中涉及的几种酶（包括VEGFR，BRAF和RET）的作用。

该研究的主要结果已于去年11月在欧洲医学肿瘤学会亚洲大会上发表，表明Tecentriq加Avastin使疾病进展或死亡的风险降低了41％（中位时间为6.8个月vs 4.3个月）。 Nexavar组的总生存期为13.2个月，但由于大多数患者还活着，因此在联合治疗组中未达到总生存期。总体缓解率（即肿瘤完全缩小或部分缩小）分别为28％和12％。

在1月份的美国临床肿瘤学会胃肠道癌症研讨会上，研究人员报告说Tecentriq加Avastin可以改善生活质量并延缓症状恶化。

Tecentriq和Avastin接收者的生活质量下降了约30％，而Nexavar接收者的生活质量下降了约40％。在身体机能和角色机能上也看到了类似的模式。对于所有这三种措施，采取联合治疗方案的患者恶化时间大大延长。使用Tecentriq加Avastin的患者也报告了更长的时间，才经历了包括食欲不振，腹泻，疲劳和疼痛在内的症状恶化。

服用Tecentriq加Avastin组的人中最常见的不良反应是高血压，疲劳和尿液中的蛋白质。使用Tecentriq加Avastin的IMbrave150参与者更容易出现发烧，肝肾生物标志物异常和输注反应，而服用Nexavar的参与者腹泻和手足综合症更多（手，足底发红，肿胀和疼痛）。脚）。

Tecentriq的推荐剂量为1,200毫克毫克，随后每三周在同一天给予每公斤Avastin 15毫克。如果停用Avastin，应每两周服用840 mg，每三周服用1200 mg或每四周服用1,680 mg Tecentriq。

“ IMbrave150研究的结果对于晚期肝癌患者是真正具有变革性的，晚期肝癌是少数几例死亡率上升且在一线治疗中选择受限的癌症之一，”戴维·格芬医学院的Richard Finn，MD加州大学洛杉矶分校强森综合癌症中心在Genentech新闻稿中说。 “自2007年以来，我们首次有了方案显着提高了索拉非尼的生存率，索拉非尼是一线肝细胞癌的一线治疗标准，并为患者提供了以良好的耐受性改善疾病控制的机会。”

健康平安猫

谢谢分享！