2015年3月25日訊 /生物谷BIOON/ --默沙東近日在黑色素瘤免疫競賽中取得偉大勝利。在一項頭對頭III期研究（KEYNOTE-006）中，該公司PD-1免疫療法Keytruda（pembrolizumab）用於晚期黑色素瘤一線治療時，療效顯著優於百時美施貴寶（BMS）免疫療法Yervoy（ipilimumab，易普利姆）。這對於百時美不斷增長的免疫專營權而言是一記重拳。目前，Keytruda已獲FDA批准用於既往經Yervoy治療的晚期黑色素瘤以及既往經一種BRAF抑制劑治療的晚期黑色素瘤。這種二三線治療，在很大程度上限制了Keytruda的患者群體。而此次Keytruda在初治晚期黑色素瘤一線治療中擊敗Yervoy，將為默沙東帶來更大的市場。
截至目前，Keytruda是首個在晚期黑色素瘤一線治療中與標準護理藥物相比表現出生存優勢的PD-1免疫療法。默沙東共研發首席Roger Perlmutter在公布這個消息時暗示，該公司有意重新建立黑色素瘤的臨床治療標準。根據官網信息，Keytruda不僅延緩了癌症的惡化，也延長了患者的生命，達到了無進展生存期（PFS）和總生存期（OS）2個主要終點。獨立數據監測委員會（IDMC）審查後認為，這些數據已經足夠好，建議終止該項III期研究。詳細的數據將在今年4月18-22日舉行的美國癌症研究協會（AACR）年會上公布。
根據此次夯實可靠的一線治療數據，默沙東已準備向FDA提交申請擴大適用人群。而根據FDA最近的表態，只要所提供的生存數據足夠強大，該機構將進行快速審查。目前PD-1/PD-L1免疫競賽領域，Keytruda的主要競爭對手是百時美的Opdivo。值得一提的是，百時美年初向FDA提交Opdivo申請僅僅4天便獲批肺癌適應症。FDA腫瘤學首席指出，Opdivo在肺癌中的總生存期數據非常出色，因此快速放行。
黑色素瘤（melanoma）是一種高度惡性腫瘤，復發率和死亡率非常高。一旦病情復發，存活率將非常低，歷史數據為11%-20%。Yervoy是一種重組人單克隆抗體，能夠有效阻斷細胞毒性T淋巴細胞相關抗原4（CTLA-4）。FDA於2011年3月批准Yervoy（3mg/kg）單藥療法用於不能手術切除或轉移性黑色素瘤患者的治療，目前該藥已獲全球40多個國家批准。（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.