PD-1/PD-L1抗癌免疫疗法竞赛异常激烈 - 药群论坛

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目前，PD-1/PD-L1免疫竞赛激烈程度无法想象，其市场峰值高达350亿美元，默沙东（Merck）、百时美施贵宝（BMS）、阿斯利康（AZN）、罗氏（Roche）均在火速推进各自的临床项目。此次竞赛中，百时美和默沙东稍微领先。百时美的PD-1抑制剂Opdivo（nivolumab）于今年7月获日本批准，是全球批准的首个PD-1抑制剂；而默沙东的PD-1抑制剂Keytruda（pembrolizumab）于今年9月初获FDA批准，是美国批准的首个PD-1抑制剂；这2种药物获批的首个适应症均为黑色素瘤。阿斯利康和罗氏的PD-L1抑制剂也已处于III期临床。

尽管研发进程相对落后，但罗氏也不甘示弱。近日，罗氏宣布，将于12月9日-13日在美国圣安东尼奥举行的第37届圣安东尼奥乳腺癌大会（SABCS）上，公布PD-L1抑制剂MPDL3280A（又名RG7446）治疗三阴乳腺癌（TNBC）的早期临床的积极数据。而默沙东紧接着表示，也将在SABCS大会上公布Keytruda治疗三阴乳腺癌（TNBC）的临床数据。

目前，尽管罗氏MPDL3280A尚未获任何监管批准，但该药已在膀胱癌、肺癌、黑色素瘤临床研究中取得可喜的成绩，此外，该公司也正在肾癌、结直肠癌和血液癌症中评价MPDL3280A的疗效。默沙东的Keytruda在胃癌和其他类型癌症中也表现出了治疗潜力。

此外，百时美也在朝乳腺癌领域进军。今年8月，百时美联手生物巨头新基（Celgene），计划启动一项I期乳腺癌临床试验，调查Opdivo与化疗药物Abraxane组合疗法的潜力。另外，值得一提的是，百时美也提交了Opdivo肺癌适应症的上市申请，标志着PD-1/PD-L1免疫疗法全球首个肺癌适应症申请，与黑色素瘤相比，肺癌尤其是有利可图的治疗领域，而百时美似乎已经抢得先机，将夺取新市场的主要份额。

PD-1/PD-L1免疫疗法是当前备受瞩目的新一类抗癌免疫疗法，旨在利用人体自身的免疫系统抵御癌症，通过阻断PD-1/PD-L1信号通路使癌细胞死亡，具有治疗多种类型肿瘤的潜力。而各大制药巨头也正在火速推进各自的项目，调查单药疗法和组合疗法用于多种癌症的治疗，以彻底发掘该类药物的最大临床潜力。

三阴乳腺癌(TNBC)特指雌激素受体（ER）、孕激素受体（PR）及人表皮生长因子受体2（HER-2）三者均为阴性表达的乳腺癌，预后极差，5年生存率不到15%。三阴乳腺癌（TNBC）对激素疗法和HER2靶向疗法（如罗氏赫赛汀Herceptin）均无效，临床治疗上主要依靠化疗。

英文原文：Merck and Roche prep breast cancer data for promising PD-1 drugs

As fervor surrounding a new class of cancer drugs builds, drug giants Merck ($MRK) and Roche ($RHHBY) are set to roll out new data for their opposing immunotherapy drugs for breast cancer by the end of the year.

Along with AstraZeneca ($AZN) and Bristol-Myers ($BMY), Merck and Roche are developing drugs designed to block a molecule called PD-1--short for programmed cell death protein 1--spurring the immune system into action to attack the tumor cells. Left unchecked, this switch allows cancerous cells to pass undetected.

Merck and Roche are hoping to widen this novel approach to treat advanced triple negative breast cancer, which is notoriously impervious to some of the most effective therapies available for breast cancer, like hormone therapy and drugs that target HER2 receptors. The New Jersey-based drugmaker and Swiss company will present early clinical results at the San Antonio Breast Cancer Symposium in December, according to Reuters.

Roche's drug, MPDL3280A, has already posted encouraging results in bladder, lung and skin cancers though it's not yet approved to treat any indications. Meanwhile, Merck is studying how triple negative breast cancer patients fair with its PD-1 drug Keyruda, which won approval for melanoma and has shown promise in stomach and other cancers.

Bristol-Myers is also moving in on this target, with its August announcement that it will begin a Phase I breast cancer trial of its PD-1 drug nivolumab alongside Celgene ($CELG) Abraxane. Bristol-Myers' drug, which it developed with partner Ono Pharmaceutical, scored a landmark approval from Japan's drug regulator in July to treat melanoma.

Bristol was also the first to submit a global regulatory nod for its PD-1 drug in lung cancer, a particularly lucrative indication, and seems well positioned to grab a major share of a new market expected to reach nearly $35 billion a year.