問答：“突破性”藥物聯合治療在肝癌患者中的生存期最長

StephenW

Q&A: Longest survival among HCC patients seen with ‘breakthrough’ drug combination
ADDED TO EMAIL ALERTS

In an exclusive interview with Healio Gastroenterology, Richard Finn, MD, discussed the results from a recent study of patients with hepatocellular carcinoma treated with combination therapy comprising atezolizumab, an immunotherapy drug and monoclonal antibody, and bevacizumab, another monoclonal antibody against the vascular endothelial growth factor (VEGF).

The data presented at the Digital Liver Cancer Summit 2021 was an update to a trial initially published with 8.6-months follow-up published in The New England Journal of Medicine. Finn, professor in the department of medicine, division of hematology/oncology, director of signal transduction and therapeutics program at the Jonsson Comprehensive Cancer at the Geffen School of Medicine at University of California, Los Angeles, and colleagues included 501 patients with HCC in the open label, randomized controlled trial. Patients received either the combination therapy of atezolizumab (Tecentriq, Genentech) plus bevacizumab (Avastin, Genentech) or sorafenib (Nexavar; Bayer) alone.

At 12 months, survival was 67.2% in the atezolizumab plus bevacizumab group, compared with 54.6% sorafenib-alone group. At 18 months, survival was 52% with atezolizumab plus bevacizumab vs. 40% with sorafenib.

Healio: What was the purpose and design of the study?

Finn: We presented updated results from the IMbrave150 study. This was a phase 3, randomized study of atezolizumab and bevacizumab vs. sorafenib in patients with advanced liver cancer. This was a frontline study for an area of unmet need because no drug or regimen had ever been shown to be superior to sorafenib since its approval in 2008 in terms of overall survival.

We randomized patients in an open-label fashion 2:1 and published the initial results The New England Journal of Medicine last May. Those data supported the global approval of the regimen starting in the U.S. in June, and since that time it’s been rolling out globally. It showed a significant improvement in overall survival but at the first analysis, the data were not mature for OS with atezolizumab and bevacozumab, meaning we did not have the true median in the treatment arm. The hazard ratio was 0.58 and the study was stopped at the first interim analysis, but we did not have longer-term follow up at that time. The study had a very nice response rate at the first analysis of 27%, and at EASL we had an initial 12 months of follow-up so now the median follow-up was over 15 and a half months.

We now present results with these updated OS data knowing that the true median for first line liver cancer with this combination therapy is over 19 months. It was 19.2 months vs. 13.4 months with sorafenib. That is a big improvement considering we’ve been trying to do this for a long time. The other updated data are that we confirmed the progression-free survival benefit. It’s maintained its separation and responses have increased. We actually have a response rate of 30% now, which includes 8% complete responses. And we have the true median duration of response, which is 18.1 months. This is coupled with the fact that there’s no new safety data concerns that showed up. It’s very consistent with the primary analysis. We also presented for the first-time detailed subgroup analysis for survival, PFS and response and we see that this benefit is very much consistent across etiologies and regions and other prognostic factors in liver cancer.

Healio: What are the key takeaways?

Finn: This doublet is probably now the standard of care for patients who have advanced liver cancer. These are patients who have disease outside the liver or disease in the liver that’s invading the vasculature or patients who have had local regional treatments that are no longer benefitting them. Systemic treatments such as this are very active and there’s no longer a need to continue to use local regional treatments beyond progression, which has been a tendency because systemic treatments haven’t offered these large gains.

Healio: What was the conclusion of the study and next step in research?

Finn: The primary analysis was what was in The New England Journal of Medicine; the stats and everything were designed for that analysis, but we will continue to follow patients for longer follow-up. There’s biomarker work being done as well, so the study’s still ongoing in that regard. It’s obviously closed to approval for some time, but there’s going to be longer-term follow-up as well.

This really sets the benchmark for front line liver cancer and that there are several other phase 3 studies we’re waiting for and those results will all be benchmarked to the results of this study.

StephenW

問答：“突破性”藥物聯合治療在肝癌患者中的生存期最長
已添加到電子郵件提醒

醫學博士理查德·芬恩（Richard Finn）在Healio胃腸病學的獨家專訪中，討論了一項針對肝細胞癌患者的近期研究結果，該患者接受了聯合療法治療，該療法包括免疫治療藥物阿特珠單抗和單克隆抗體以及另一種抗血管內皮生長的單克隆抗體貝伐單抗因子（VEGF）。

在2021年數字肝癌峰會上提供的數據是對一項試驗的更新，該試驗最初在8.6個月的後續研究中發表於《新英格蘭醫學雜誌》上。芬蘭大學血液學/腫瘤學系教授，信號傳導和治療項目主任，芬蘭加利福尼亞大學洛杉磯分校格芬醫學院的芬恩教授和同事在該研究中納入了501例HCC患者開放標籤，隨機對照試驗。患者單獨接受Atezolizumab（Tecentriq，Genentech）加貝伐單抗（Avastin，Genentech）或索拉非尼（Nexavar; Bayer）的聯合治療。

Atezolizumab聯合貝伐單抗組在12個月時的生存率為67.2％，而索拉非尼單藥組的生存率為54.6％。 18個月時，atezolizumab加貝伐單抗的生存率為52％，而索拉非尼為40％。

Healio：研究的目的和設計是什麼？

Finn：我們介紹了IMbrave150研究的最新結果。這是晚期肝癌患者中atezolizumab和bevacizumab與sorafenib的3期隨機研究。這是針對未滿足需求的領域的前線研究，因為自2008年批准索拉非尼以來，沒有任何藥物或方案在總生存率方面優於索拉非尼。

我們以開放標籤的方式2：1將患者隨機分組，並於去年五月發表了《新英格蘭醫學雜誌》的初步結果。這些數據支持了該方案從6月在美國開始的全球批准，自那時以來一直在全球推廣。它顯示了總體生存率的顯著改善，但在最初的分析中，使用阿扎佐珠單抗和貝伐單抗的OS的數據尚不成熟，這意味著我們在治療組中沒有真正的中位數。風險比為0.58，研究在第一個中期分析中被終止，但當時我們沒有長期隨訪。這項研究在最初的分析中有27％的良好答复率，而在EASL，我們進行了最初的12個月的隨訪，因此現在的中位隨訪時間超過15個半月。

現在，我們知道這些聯合治療的一線肝癌的真實中位數超過19個月，這些更新的OS數據可得出結果。相較於索拉非尼的13.4個月為19.2個月。考慮到我們已經嘗試了很長時間了，所以這是一個很大的進步。其他更新的數據是我們證實了無進展生存獲益。它保持了分離狀態，反響有所增加。實際上，我們現在的回應率為30％，其中包括8％的完整回應。而且我們有真實的響應時間中位數，即18.1個月。再加上沒有新的安全數據問題出現的事實。這與主要分析非常一致。我們還首次對生存，PFS和反應進行了詳細的亞組分析，我們發現這種益處在肝癌的病因和地區以及其他預後因素中非常一致。

Healio：關鍵要點是什麼？

Finn：現在，這種雙重治療可能已經成為晚期肝癌患者的標準治療方法。這些是患有肝外疾病或侵襲脈管系統的肝臟疾病的患者，或者接受了不再使他們受益的局部區域性治療的患者。諸如此類的全身治療非常活躍，不再需要繼續使用局部區域治療，而不是繼續發展，這已成為一種趨勢，因為全身治療並未帶來如此大的收益。

Healio：研究的結論和下一步的研究是什麼？

Finn：主要分析是《新英格蘭醫學雜誌》上的內容；統計信息和所有內容均專為該分析而設計，但我們將繼續關注患者以進行更長的隨訪。生物標記物的工作也在完成中，因此該研究仍在進行中。顯然，它尚待批准一段時間，但還將進行長期跟踪。

這確實為一線肝癌樹立了標杆，還有其他一些我們正在等待的其他3期研究，這些結果都將以此研究為基準。