派姆單抗降低三期黑色素瘤的復(fù)發(fā)
本文于2018年4月15日發(fā)表于AACR網(wǎng)站，翻譯僅供參考！
芝加哥---4月14-18日的AACR年會上，KEYNOTE-054/EORTC 1325-MG三期臨床試驗研究表明，經(jīng)過一整年的共18劑派姆單抗給藥治療后，三期黑色素瘤病人術(shù)后復(fù)發(fā)率大幅度下降。
該研究同時發(fā)布在了新英格蘭醫(yī)學(xué)雜志上。
法國維勒瑞夫大巴黎Gustave Roussy癌癥中心主任Alexander M. M. Eggermont醫(yī)學(xué)博士告訴我們：“三期黑色素瘤病人在一個或多個局部淋巴結(jié)處患有轉(zhuǎn)移性疾病。病人的復(fù)發(fā)風(fēng)險決定于患病的淋巴結(jié)數(shù)量和腫瘤負(fù)荷。復(fù)發(fā)風(fēng)險高的病人，其一個或多個區(qū)域淋巴結(jié)呈黑色素轉(zhuǎn)移狀態(tài)。單個陽性淋巴結(jié)，其直徑遠(yuǎn)大于1毫米?！?/span>
Eggermont博士表示：“我們很高興，佐劑派姆單抗可以起到成效。術(shù)后一年內(nèi)，每三周給藥一次，每次200毫克，一年18次給藥后，腫瘤全切的三期黑色素瘤病人的復(fù)發(fā)率大大降低。希望美國和歐洲國家的相關(guān)政府管理人員能看到這一研究發(fā)現(xiàn)，并批準(zhǔn)使用派姆單抗作為這類病人的新療法。
隨機分配到派姆單抗組的病人，其術(shù)后12個月無復(fù)發(fā)存活率為75.4%，而隨機分配到安慰劑組的病人，這一數(shù)字為61.0%。整體來看，派姆單抗組的病人的復(fù)發(fā)率下降了43%。
FDA分別于2015年10月和2017年12月批準(zhǔn)使用ipilumumab (Yervoy)和nivolumab (Opdivo)用于全切高風(fēng)險三期黑色素瘤病人的術(shù)后治療佐劑。
Eggermont博士和同事們在KEYNOTE-054/EORTC 1325-MG三期臨床試驗中，對1019名腫瘤全切高復(fù)發(fā)風(fēng)險三期黑色素瘤病人進(jìn)行試驗，1:1將他們隨機分配至派姆單抗組和安慰劑組，每三周進(jìn)行一次200毫克的給藥，共18次給藥（中途如發(fā)生復(fù)發(fā)或產(chǎn)生不可耐受的毒性反應(yīng)，則立即停止給藥）。
取中值1.25年的跟蹤觀察后，隨機派姆單抗組的全部514名病人中有135名病人復(fù)發(fā)或死亡，隨機安慰劑組的全部505名病人中有216名病人復(fù)發(fā)或死亡。
PD-L1陽性和PD-L1陰性的腫瘤單獨分析時，派姆單抗產(chǎn)生的效力相似。在852名帶有PD-L1陽性腫瘤的病人中，隨機派姆單抗組的病人，其復(fù)發(fā)率或死亡率相較于隨機安慰劑組下降46%。在116名帶有PD-L1陰性腫瘤的病人中，隨機派姆單抗組的病人，其復(fù)發(fā)率或死亡率相較于隨機安慰劑組下降53%。
Eggermont 博士說：“這次試驗的重要點在于隨機安慰劑組的病人復(fù)發(fā)后可獲得派姆單抗的治療。這種跨界的試驗設(shè)計在黑色素瘤的佐劑試驗中是的，我們從中可以分析出派姆單抗的應(yīng)用是在術(shù)后立刻開始比較好，還是在復(fù)發(fā)發(fā)生時開始比較好?！?/span>
從Eggermont博士那里還了解到，這項研究的主要不足之處是，目前我們尚需更多時間來判斷現(xiàn)階段得到的防復(fù)發(fā)的良好效果可以從整體上提高病人的存活率。
這項研究由歐洲癌癥研究和治療組織（EORTC）執(zhí)行，由默克贊助。Eggermont獲得了為科學(xué)咨詢委員會和數(shù)據(jù)監(jiān)督委員會準(zhǔn)備的酬謝金，酬謝金出資方為Actelion、Agenus、Bayer、Bristol-Myers Squibb、GlaxoSmithKline、HalioDx、Incyte、ISA Pharmaceuticals、Merck、Merck Serono、Nektar、Novartis、Pfizer和Sanofi。
English Version
Pembrolizumab Reduced the Risk for Recurrence of Stage 3 Melanoma
CHICAGO — A one-year course of 18 doses of pembrolizumab (Keytruda) significantly reduced the risk of recurrence for patients with stage 3 melanoma who were at high risk of recurrence after surgery, according to data from the KEYNOTE-054/EORTC 1325-MG phase III clinical trial, presented at the AACR Annual Meeting 2018, April 14–18.
This study is being published simultaneously in The New England Journal of Medicine.
"Patients with stage 3 melanoma have metastatic disease in one or more regional lymph nodes,"said Alexander M. M. Eggermont, MD, PhD, director general of Gustave Roussy Cancer Campus Grand Paris in Villejuif, France. "A patient’s risk of recurrence depends on the number of lymph nodes affected and the tumor load. Those classified as having a high risk of recurrence have one or more regional lymph nodes with melanoma metastasis. In the case of a single positive node, the diameter must be greater than 1 millimeter."
"We were pleased to see that adjuvant pembrolizumab, given as a flat dose of 200 milligrams every three weeks after surgery for up to a year, which is 18 doses, significantly reduced the risk of recurrence for patients with high-risk stage 3 melanoma that has been completely resected," continued Eggermont. "We hope that these data will lead to regulators in the United States and Europe approving pembrolizumab as a new treatment option for these patients."
For all the patients randomized to pembrolizumab, the 12-month recurrence-free survival rate was 75.4 percent, compared with 61.0 percent for all those randomized to placebo. Thus, overall, patients randomized to pembrolizumab were 43 percent less likely to have recurrence.
The FDA approved ipilumumab (Yervoy) and nivolumab (Opdivo) for use as an adjuvant treatment for patients with high-risk stage 3 melanoma that has been completely resected in October 2015 and December 2017, respectively.
Eggermont and colleagues enrolled 1,019 patients with stage 3 melanoma who were at high risk of recurrence after complete resection of their tumors in the KEYNOTE-054/EORTC 1325-MG phase III clinical trial. Patients were randomized 1:1 to a flat dose of 200 milligrams of pembrolizumab or placebo every three weeks for a total of 18 doses or until disease recurrence or unacceptable toxicity.
After a median follow-up of 1.25 years, 135 of the 514 patients randomized to pembrolizumab and 216 of the 505 patients randomized to placebo had been diagnosed with recurrent disease or had died.
The benefits of pembrolizumab were similar when patients with PD-L1-positive and PD-L1-negative tumors were analyzed separately. Among the 852 patients with PD-L1-positive tumors, those randomized to pembrolizumab were 46 percent less likely to have a recurrence or death event compared with those randomized to placebo. Among the 116 patients with PD-L1-negative tumors, those randomized to pembrolizumab were 53 percent less likely to have a recurrence or death event.
"An important aspect of this trial is that patients randomized to placebo who have recurrence are offered access to pembrolizumab," said Eggermont. "This cross-over design is unique in the world of adjuvant trials in melanoma and will permit us to analyze if adjuvant therapy with pembrolizumab right after surgery is better or not than treating only those who relapse and start treatment at relapse."
According to Eggermont, the main limitation of the study is that we need more time before we can determine whether these positive recurrence-free survival results will lead to improvement in overall survival for the patients.
This study was conducted by the European Organisation for Research and Treatment of Cancer (EORTC) and sponsored by Merck. Eggermont has received honoraria for scientific advisory board and data monitoring board functions from Actelion, Agenus, Bayer, Bristol-Myers Squibb, GlaxoSmithKline, HalioDx, Incyte, ISA Pharmaceuticals, Merck, Merck Serono, Nektar, Novartis, Pfizer, and Sanofi.
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