在無法切除的肝癌中，HAIC的生存率優於標準TACE

StephenW

Survival Improved With HAIC Over Standard TACE in Unresectable HCCSeptember 20, 2020
Danielle Ternyila

Conference | ESMO Congress

A significant improvement in overall survival was observed with the addition of hepatic arterial infusion chemotherapy to oxaliplatin, fluorouracil, and leucovorin compared with transarterial chemoembolization in patients with unresectable hepatocellular carcinoma.



A significant improvement in overall survival (OS) was observed with the addition of hepatic arterial infusion chemotherapy (HAIC) to oxaliplatin, fluorouracil, and leucovorin (FOLFOX) compared with transarterial chemoembolization (TACE) as treatment of patients with unresectable hepatocellular carcinoma (HCC), according the results from a study presented during the 2020 ESMO Virtual Congress.
The randomized phase 3, multi-center, open-label trial conducted in China included 315 patients who either received HAIC (n = 159) or TACE (n = 156). Patients were mostly men, at least 18 years old, with a primary HCC tumor measuring more than 7 centimeters, and had an ECOG performance status of 0 or 1. The majority of participants (90%) had hepatitis B infection, 60% had confirmed liver cirrhosis, and about half of patients had more than 3 lesions.
“The patient demographics were generally similar across arms and are representative of our Chinese intermediate-staged HCC population,” study author Ming Shi, MD, PhD, Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, in Guangzhou, China, said during the virtual meeting.
Currently, TACE is the standard of care for patients with unresectable intermediate-stage HCC, and a previous phase II study demonstrated higher treatment response with HAIC with FOLFOX versus TACE, according to Shi.
“Intermediate or BCLC B stage HCC is a largely heterogenous group that includes patients who do not benefit from TACE—the standard of care—with a median overall survival of only 9 to 13 months,” Lorenza Rimassa, MD, associate professor of medical oncology, Humanitas University and Humanitas Research Hospital-IRCCS in Milan, Italy, said in a discussion following the presentation. “This represents an important unmet clinical need and new data are strongly needed.”
Investigators of this trial examined OS as their primary endpoint, with secondary endpoints of objective response rate (ORR) using RECIST criteria, progression-free survival (PFS), and safety. Treatment response was also assessed using mRECIST.
The patients were randomized 1:1 to HAIC (oxaliplatin 130 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2) on day 1 and fluorouracil infusion 2400 mg/m2 for 24 hours, every 3 weeks via repeated catheterization up to 6 cycles, or TACE (50 mg of epirubicin, 50 mg of lobaplatin, and lipiodol and polyvinyl alcohol particles) on demand. Treatment was continued until tumor progression or intolerable toxicity.
An average of 4 sessions were received by patients in the HAIC arm, whereas patients in the TACE arm received an average of 2 sessions. Treatment crossover occurred between both arms with 8 patients crossing over from HAIC to TACE and 20 patients crossing over from TACE to HAIC.
“There was no significant difference in the number of patients receiving either subsequent treatment between the 2 arms,” Shi said.
Patients who received HAIC saw a higher median OS compared with those who received TACE (23.1 months [95% CI, 18.23-27.97] versus 16.07 months [95% CI, 14.26-17.88], respectively). Hazard ratio was 0.58 (95% CI, 0.45-0.75; P <0.001).
In addition, compared with the TACE arm, patients in the HAIC arm had a higher ORR (RECIST: 45.9% versus 17.9%, P <0.001; mRECIST: 48.4% versus 32.7%, P = .004). Median PFS was also longer at 9.63 months (95% CI, 7.40-11.86) in the HAIC group compared with 5.4 months (95% CI, 3.82-6.98) in the TACE group.
“We can appreciate that overall survival is longer than expected in the TACE arm, overall survival curves seem to separate after 6 months, [and] progression-free survival curves seem to separate from the beginning,” Ramissa said. “So we have further questions, is there an impact of the crossover? And which is the median duration of the treatment? And we don’t have the answers.”
More patients in the HAIC group underwent subsequent resection compared with the TACE group (23.8% versus 11.5%, P = 0.004).
Although both groups experienced serious adverse events (AEs), HAIC had a better safety profile compared with TACE, Shi said. Serious AEs occurred in the TACE arm (30%) versus the HAIC arm (19%). These included ascites, hyperbilirubinemia, upper gastrointestinal bleeding, cholangitis, and infection. However, the HAIC group experienced more occurrences of thrombocytopenia, neutropenia, and diarrhea. Two treatment-related grade 5 events were seen in each arm.
Although Rimassa called the data encouraging, she believes there are still many unanswered questions, such as “Can this treatment be extrapolated to other patient populations? My answer is no,” she said.
The cut-off for the present analysis was April 2020 and patient follow-up is on-going.
“HAIC is not a globally accepted treatment for HCC,” Rimassa said regarding trial design. “It is mainly used in China where this trial has been conducted and more clinical trials are needed to define it’s true.”
Reference
Shi M, Li Q, He M, et al. Hepatic arterial infusion chemotherapy with oxaliplatin, fluorouracil, and leucovorin versus transarterial chemoembolization for unresectable hepatocellular carcinoma: A randomised phase III trial. Presented at: 2020 ESMO Virtual Congress; September 19-21, 2020; Virtual. Abstract 981O.

StephenW

在無法切除的肝癌中，HAIC的生存率優於標準TACE
2020年9月20日
丹妮爾·特妮拉（Danielle Ternyila）

會議| ESMO大會

在無法切除的肝細胞癌患者中，與經動脈化學栓塞相比，在奧沙利鉑，氟尿嘧啶和亞葉酸鈣中添加肝動脈灌注化療與整體動脈化療相比，可顯著改善總生存期。

與經動脈化學栓塞術（TACE）相比，將奧沙利鉑，氟尿嘧啶和亞葉酸鈣（FOLFOX）加肝動脈灌注化療（HAIC）治療無法切除的肝細胞癌（HCC）患者，可觀察到總體生存（OS）的顯著改善。 ，根據2020年ESMO虛擬大會上提出的研究結果。

在中國進行的隨機第3期，多中心，開放標籤試驗包括315例接受HAIC（n = 159）或TACE（n = 156）的患者。患者多為男性，至少18歲，原發性HCC腫瘤超過7厘米，ECOG表現為0或1。大多數參與者（90％）患有乙型肝炎感染，其中60％已確認肝硬化，大約一半的患者有3個以上的病變。

研究作者Ming Shi，醫學博士，中山大學附屬腫瘤防治中心肝膽腫瘤科醫師，“中國各年齡階段的肝癌人群總體上是相似的，代表了我們的中國中期肝癌人群。”在虛擬會議上說。

目前，TACE是不可切除的中期HCC患者的標準治療方法，Shi表示，先前的II期研究表明FOLFOX聯合HAIC治療較TACE有更高的治療反應。

“中級或BCLC B期肝癌是一個異質性人群，其中包括不能從TACE（標準治療）中受益的患者，其平均總生存期僅為9到13個月，”醫學腫瘤學副教授Lorenza Rimassa博士演講後的討論中，位於意大利米蘭的Humanitas大學和Humanitas研究醫院-IRCCS表示。 “這代表了一個重要的未滿足的臨床需求，並且迫切需要新的數據。”

該試驗的研究者將OS作為其主要終點，並使用RECIST標準，無進展生存期（PFS）和安全性作為客觀終點應答率（ORR）的次要終點。還使用mRECIST評估了治療反應。

患者在第1天以1：1的比例隨機分配至HAIC（奧沙利鉑130 mg / m2，亞葉酸400 mg / m2，氟尿嘧啶推注400 mg / m2）和氟尿嘧啶2400 mg / m2輸注24小時，每3週通過反复的導管插入術至6個週期，或按需使用TACE（50 mg表柔比星，50 mg洛鉑，以及碘油和聚乙烯醇顆粒）。繼續治療直到腫瘤進展或無法忍受的毒性。

HAIC組患者平均接受4次治療，而TACE組患者平均接受2次治療。治療交叉發生在兩個手臂之間，其中8例從HAIC越過TACE，20例從TACE越過HAIC。

“這兩個手臂之間接受任何後續治療的患者數量沒有顯著差異，”施說。

與接受TACE的患者相比，接受HAIC的患者的中位OS更高（分別為23.1個月[95％CI，18.23-27.97]與16.07個月[95％CI，14.26-17.88]）。危險比為0.58（95％CI，0.45-0.75; P <0.001）。

此外，與TACE組相比，HAIC組患者的ORR更高（RECIST：45.9％比17.9％，P <0.001； mRECIST：48.4％比32.7％，P = .004）。 HAIC組的中位PFS也更長，為9.63個月（95％CI，7.40-11.86），而TACE組為5.4個月（95％CI，3.82-6.98）。

Ramissa說：“我們可以理解，TACE組的總生存期比預期的要長，總生存曲線似乎在6個月後分離，並且無進展生存曲線似乎與開始分離。” “因此，我們還有其他問題，交叉是否會產生影響？療程的中位數是多少？而且我們沒有答案。”

與TACE組相比，HAIC組中接受手術的患者更多（23.8％對11.5％，P = 0.004）。

Shi說，儘管兩組都經歷了嚴重的不良事件（AEs），但與TACE相比，HAIC的安全性更高。 TACE組（30％）與HAIC組（19％）發生嚴重AE。這些包括腹水，高膽紅素血症，上消化道出血，膽管炎和感染。但是，HAIC組的血小板減少症，中性粒細胞減少和腹瀉發生率更高。每隻手臂出現兩次與治療相關的5級事件。
儘管Rimassa認為數據令人鼓舞，但她仍然認為仍有許多未解決的問題，例如“這種治療方法可以推廣到其他患者人群嗎？ 我的回答是不。”她說。

當前分析的截止日期是2020年4月，患者的隨訪正在進行中。

Rimassa談到試驗設計時說：“ HAIC不是HCC的全球公認治療方法。” “它主要在已經進行了該試驗的中國使用，需要更多的臨床試驗才能確定其正確性。”

參考

Shi M，Li Q，He M等。 奧沙利鉑，氟尿嘧啶和亞葉酸肝動脈灌注化療與經動脈化學栓塞治療無法切除的肝細胞癌：一項隨機III期試驗。 提出於：2020 ESMO虛擬大會； 2020年9月19日至21日； 虛擬。 摘要981O。