根據(jù)周三公布的初步試驗結(jié)果，由羅氏（Roche）開發(fā)的一種實驗性藥物MPDL3280A，針對數(shù)種腫瘤均表現(xiàn)出了令人印象深刻的療效，同時耐受性良好。盡管相關(guān)臨床測試仍處于早期階段，但該藥已被認為是羅氏最有前途的新一代免疫療法（ immunotherapies）之一。
根據(jù)I期臨床研究的數(shù)據(jù)，在140例晚期黑色素瘤、肺癌、腎細胞癌患者中，經(jīng)MPDL3280A治療后，有21%（29例）的患者腫瘤顯著縮小。這29例患者中，在啟動治療一年多之后，仍有26例繼續(xù)對MPDL3280A治療響應(yīng)。該項研究的詳細數(shù)據(jù)將提交至6月初在芝加哥舉行的美國臨床腫瘤學(xué)會會議。
德意志銀行（Deutsche Bank）分析師Tim Race在一份研究報告中稱，手握MPDL3280A，羅氏潛在地擁有了一個市值超50億美元且具有橫跨數(shù)種腫瘤持續(xù)性利益的產(chǎn)品。
MPDL3280A是一種基因工程抗體，靶向于腫瘤細胞上的一種名為PD-L1的蛋白，腫瘤利用這種防御機制欺騙機體免疫系統(tǒng)中的T細胞，使之保持失活（inactive）狀態(tài)。一旦T細胞能夠識別腫瘤，它們能夠生長和繁殖并更有效地攻擊癌細胞。
“我們已經(jīng)在肺癌、腎癌、黑色素瘤中看到了實實在在的驚人反應(yīng)，”該研究的首席研究員Roy Herbst博士在接受記者采訪時說道。
所提供的數(shù)據(jù)顯示，到目前為止，MPDL3280A在黑色素瘤、肺癌、腎細胞癌中的響應(yīng)率分別為31%、22%、13%。
目前，該項研究已經(jīng)被擴大至結(jié)腸癌、膀胱癌、頭頸部癌癥患者。
未觀察到嚴重副作用
MPDL3280A通過靜脈注射給藥，每三周給藥一次，該藥所攻擊的靶標與百時美施貴寶（BMS）、默沙東（Merck & Co）及其他制藥公司等所開發(fā)的非常有前途的免疫療法PD-1抑制劑靶標不同。
羅氏及一些研究人員相信，抗PDL1藥物比抗PD-1藥物具有更高的選擇性，并可能減少肺臟及其他器官的炎癥。
在該項研究中，MPDL3280A耐受性良好，沒有出現(xiàn)需要限制劑量的副作用。大多數(shù)的不良事件都是短暫性且不嚴重的。研究中未在任何患者中觀察到肺部炎癥。
“有關(guān)無進展生存期（PFS）或癌癥惡化前的平均時間數(shù)據(jù)，目前尚未完成。將需要一段時間來決定患者的整體生存率。但迄今獲得的數(shù)據(jù)令人信服。與歷史對照組（historical controls）相比，該項研究中難治性肺癌、黑色素瘤、腎癌患者的無進展生存期數(shù)據(jù)令人印象深刻，”Roy Herbst博士說道。“這是一個非常有趣的癌癥治療方法，我們目前也仍在學(xué)習如何正確的選擇病人。”
為了實現(xiàn)這一目標，羅氏目前正在開發(fā)一種診斷工具，來鑒別哪些患者（如PDL1蛋白檢測陽性）最有可能從MPDL3280A治療中受益。
根據(jù)試驗結(jié)果，羅氏稱，將在非小細胞肺癌（NSCLC）患者中啟動一項更大的研究，該研究的數(shù)據(jù)將用于支持MPDL3280A的監(jiān)管批準。
英文原文：Roche immunotherapy shows response over range of cancers
(Reuters) - An experimental Roche Holding AG drug that helps the immune system attack tumors was well tolerated and demonstrated an impressive effect against a variety of cancers, according to preliminary trial results released on Wednesday.
While clinical testing of the drug is still in its early phases, the Roche treatment is considered one of the most promising in a new class of immunotherapies being developed by global drugmakers.
The drug, called MPDL3280A, significantly shrank tumors in 21 percent of 140 patients with advanced melanoma, lung cancer or kidney cancer, according to data from a scientific abstract of the Phase I study. Of the 29 patients whose cancer responded to the drug, 26 continued to respond - some more than a year after starting treatment - researchers said.
The study will be presented at the American Society of Clinical Oncology meeting in Chicago in early June.
Deutsche Bank analyst Tim Race, in a research note, said with this drug Roche "potentially has a greater than $5 billion product with potential for durable benefit across multiple cancers."
Roche's drug is an engineered antibody that targets a protein called PD-L1 on cancerous tumors, a defense mechanism that tumors use to trick the immune system's T cells into remaining inactive. Once the T cells can recognize the cancer, they grow and multiply to more efficiently attack it.
"We have seen really amazing responses in lung cancer, in kidney cancer, in melanoma," Dr Roy Herbst, the study's lead investigator, said in an interview.
Broken down by cancer type, the response rate so far has been 31 percent in melanoma, 22 percent in lung cancer and 13 percent in kidney cancer, the available data showed.
The study has since been expanded to include patients with colon, bladder and head and neck cancers, researchers said.
NO SERIOUS SIDE EFFECTS SEEN
MPDL3280A, which was administered intravenously every three weeks, attacks a different target than a similar class of highly promising immunotherapies called PD-1 inhibitors being developed by Bristol-Myers Squibb, Merck & Co and others.
Roche and some researchers believe the anti-PDL1 medicine is more selective than the PD-1 drugs and may lead to less inflammation of the lung and other organs.
The Roche drug was well tolerated in the study, Herbst said: There were no side effects that required limiting the dosing.
"Most of the adverse events were transient and of low significance. We haven't seen any patients with significant inflammation of lung," said Herbst, chief of medical oncology at Yale Cancer Center in New Haven, Connecticut.
The data on progression-free survival, or the average time before a cancer begins to worsen, was not yet complete, and it will be a while before an overall survival benefit can be determined. But Herbst found the results thus far compelling.
"The progression-free survival for refractory lung, melanoma and renal cancers is impressive compared to historical controls," he said. "This is an incredibly interesting approach for cancer. It's showing efficacy. We're still learning how to select the patients properly."
Toward that end Roche is developing a diagnostic tool to identify those most likely to benefit from the treatment, such as those who test positive for the PDL1 protein.
Based on the trial's results, Roche said it will begin a larger study of its anti-PDL1 drug in patients with non-small-cell lung cancer that could be used to seek approval of the medicine.
