根据周三公布的初步试验结果，由罗氏（Roche）开发的一种实验性药物MPDL3280A，针对数种肿瘤均表现出了令人印象深刻的疗效，同时耐受性良好。尽管相关临床测试仍处于早期阶段，但该药已被认为是罗氏最有前途的新一代免疫疗法（ immunotherapies）之一。
根据I期临床研究的数据，在140例晚期黑色素瘤、肺癌、肾细胞癌患者中，经MPDL3280A治疗后，有21%（29例）的患者肿瘤显着缩小。这29例患者中，在启动治疗一年多之后，仍有26例继续对MPDL3280A治疗响应。该项研究的详细数据将提交至6月初在芝加哥举行的美国临床肿瘤学会会议。
德意志银行（Deutsche Bank）分析师Tim Race在一份研究报告中称，手握MPDL3280A，罗氏潜在地拥有了一个市值超50亿美元且具有横跨数种肿瘤持续性利益的产品。
MPDL3280A是一种基因工程抗体，靶向于肿瘤细胞上的一种名为PD-L1的蛋白，肿瘤利用这种防御机制欺骗机体免疫系统中的T细胞，使之保持失活（inactive）状态。一旦T细胞能够识别肿瘤，它们能够生长和繁殖并更有效地攻击癌细胞。
“我们已经在肺癌、肾癌、黑色素瘤中看到了实实在在的惊人反应，”该研究的首席研究员Roy Herbst博士在接受记者采访时说道。
所提供的数据显示，到目前为止，MPDL3280A在黑色素瘤、肺癌、肾细胞癌中的响应率分别为31%、22%、13%。
目前，该项研究已经被扩大至结肠癌、膀胱癌、头颈部癌症患者。
未观察到严重副作用
MPDL3280A通过静脉注射给药，每三周给药一次，该药所攻击的靶标与百时美施贵宝（BMS）、默沙东（Merck & Co）及其他制药公司等所开发的非常有前途的免疫疗法PD-1抑制剂靶标不同。
罗氏及一些研究人员相信，抗PDL1药物比抗PD-1药物具有更高的选择性，并可能减少肺脏及其他器官的炎症。
在该项研究中，MPDL3280A耐受性良好，没有出现需要限制剂量的副作用。大多数的不良事件都是短暂性且不严重的。研究中未在任何患者中观察到肺部炎症。
“有关无进展生存期（PFS）或癌症恶化前的平均时间数据，目前尚未完成。将需要一段时间来决定患者的整体生存率。但迄今获得的数据令人信服。与历史对照组（historical controls）相比，该项研究中难治性肺癌、黑色素瘤、肾癌患者的无进展生存期数据令人印象深刻，”Roy Herbst博士说道。“这是一个非常有趣的癌症治疗方法，我们目前也仍在学习如何正确的选择病人。”
为了实现这一目标，罗氏目前正在开发一种诊断工具，来鉴别哪些患者（如PDL1蛋白检测阳性）最有可能从MPDL3280A治疗中受益。
根据试验结果，罗氏称，将在非小细胞肺癌（NSCLC）患者中启动一项更大的研究，该研究的数据将用于支持MPDL3280A的监管批准。
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.
