默沙东免疫疗法Keytruda黑色素瘤一线治疗击败百时美Yervoy

默沙东近日在黑色素瘤免疫竞赛中取得伟大胜利。在一项头对头III期研究（KEYNOTE-006）中，该公司PD-1免疫疗法Keytruda（pembrolizumab）用于晚期黑色素瘤一线治疗时，疗效显著优于百时美施贵宝（BMS）免疫疗法Yervoy（ipilimumab，易普利姆）。这对于百时美不断增长的免疫专营权而言是一记重拳。目前，Keytruda已获FDA批准用于既往经Yervoy治疗的晚期黑色素瘤以及既往经一种BRAF抑制剂治疗的晚期黑色素瘤。这种二三线治疗，在很大程度上限制了Keytruda的患者群体。而此次Keytruda在初治晚期黑色素瘤一线治疗中击败Yervoy，将为默沙东带来更大的市场。

截至目前，Keytruda是首个在晚期黑色素瘤一线治疗中与标准护理药物相比表现出生存优势的PD-1免疫疗法。默沙东共研发首席Roger Perlmutter在公布这个消息时暗示，该公司有意重新建立黑色素瘤的临床治疗标准。根据官网信息，Keytruda不仅延缓了癌症的恶化，也延长了患者的生命，达到了无进展生存期（PFS）和总生存期（OS）2个主要终点。独立数据监测委员会（IDMC）审查后认为，这些数据已经足够好，建议终止该项III期研究。详细的数据将在今年4月18-22日举行的美国癌症研究协会（AACR）年会上公布。

根据此次夯实可靠的一线治疗数据，默沙东已准备向FDA提交申请扩大适用人群。而根据FDA最近的表态，只要所提供的生存数据足够强大，该机构将进行快速审查。目前PD-1/PD-L1免疫竞赛领域，Keytruda的主要竞争对手是百时美的Opdivo。值得一提的是，百时美年初向FDA提交Opdivo申请仅仅4天便获批肺癌适应症。FDA肿瘤学首席指出，Opdivo在肺癌中的总生存期数据非常出色，因此快速放行。

黑色素瘤（melanoma）是一种高度恶性肿瘤，复发率和死亡率非常高。一旦病情复发，存活率将非常低，历史数据为11%-20%。Yervoy是一种重组人单克隆抗体，能够有效阻断细胞毒性T淋巴细胞相关抗原4（CTLA-4）。FDA于2011年3月批准Yervoy（3mg/kg）单药疗法用于不能手术切除或转移性黑色素瘤患者的治疗，目前该药已获全球40多个国家批准。（生物谷Bioon.com）

英文原文：Merck's Keytruda bests BMS' Yervoy in head-to-head melanoma trial

Trial stopped early after Keytruda hit both survival goals

Advantage Merck ($MRK) in the melanoma immunotherapy race. The U.S.-based company says its PD-1 drug Keytruda met its goals in a head-to-head study with Bristol-Myers Squibb's ($BMY) Yervoy (ipilimumab), dealing a blow to that company's growing immunotherapy franchise.

Even better, Keytruda bested Yervoy in previously untreated patients with advanced melanoma, a result that could lead to a bigger market for the Merck med.

Keytruda hit its primary endpoints not only for stalling cancer progression, but for extending patients' lives--so-called overall survival, a key measure for regulators, doctors and payers. Merck stopped the study, called KEYNOTE-006, after trial monitors decided the results were strong enough to prompt a halt.

Currently, Keytruda is approved for patients with advanced melanoma previously treated with Yervoy and, in some patients, another type of drug as well. That second- and third-line status limits the number of patients eligible for the drug.

With solid data on first-line use, Merck could ask the FDA to expand that patient pool--and with recent decisions, the agency has proved willing to decide quickly, provided the survival data is there. Keytruda's rival immunotherapy Opdivo recently won an indication in lung cancer mere days after Bristol-Myers filed for that approval, and the FDA's oncology chief cited its impressive overall survival numbers for the quick move.

Opdivo's lung cancer nod put Bristol-Myers ahead in that field, at least in squamous non-small cell lung cancer (NSCLC) patients. Keytruda is eying an NSCLC indication as well, and given the data at hand, the Merck med may get an FDA approval covering a broader range of patients. That won't happen till later this year, however.

Now, Merck has an edge in melanoma, and it's ready to brag about it. The drug delivered a "statistically significant and clinically meaningful improvement" in overall survival and progression-free survival" compared to Yervoy, the company said in a statement. And in announcing the trial results, R&D chief Roger Perlmutter hinted at possible standard-of-care movement. "Evidence from our clinical program for Keytruda will help to define the appropriate treatment of advanced melanoma," Perlmutter said in the statement.

Next month, we'll get a better idea of how big Keytruda's melanoma advantage is. Full data from the KEYNOTE-006 study will be unveiled at the American Association of Cancer Research meeting in Philadelphia.