PD-1免疫疗法能治疗鼻咽癌吗？——这些药一直在路上

近日，君实生物与其合作伙伴Coherus Biosciences联合宣布，已完成向美国食品和药物管理局（FDA）滚动提交（Rolling review）特瑞普利单抗注射液（toripalimab，商品名：拓益）治疗鼻咽癌（NPC）的生物制品许可申请（BLA）：联合吉西他滨/顺铂作为晚期复发或转移性鼻咽癌患者的一线治疗和单药用于复发或转移性鼻咽癌含铂化疗后的二线及以上治疗。这也意味着，PD-1免疫疗法在治疗鼻咽癌的道路上又前进了一步。

PD-1（programmed death 1），称作程序性死亡受体1，是一种重要的免疫抑制分子，它通过向下调节免疫系统对人体细胞的反应，以及抑制T细胞炎症活动来调节免疫系统并促进自身耐受。PD-1的这种作用可以预防自身免疫性疾病，但也会防止免疫系统杀死癌细胞。PD-1抑制剂的作用就是激活免疫系统，然后发现肿瘤并杀死它们。

肿瘤免疫治疗中常用的K药和O药，都属于PD-1抑制剂类药物，它们在临床上已经获批治疗多种血液肿瘤和实体肿瘤适应症，但目前尚未有一种PD-1药物被FDA获批治疗鼻咽癌。

鼻咽癌是一种发生于鼻咽部黏膜上皮的恶性肿瘤，是常见的头颈部恶性肿瘤之一。据世界卫生组织（WHO）统计，2020年鼻咽癌在全球范围内确诊的新发病例数超过13万，其中近半数的鼻咽癌发生在我国。因其高发地区在我国主要集中于广东、广西、湖南、福建和江西等南方省份，尤其是广东，所以鼻咽癌又有“广东癌”之称。

早期鼻咽癌治疗首选放疗，治疗效果良好，90%的患者可以治愈或者长期无瘤生存。然而，鼻咽癌临床症状复杂多样，容易导致鼻咽癌被漏诊或误诊。有数据显示，约80%的患者临床确诊时大多已进入中晚期，出现淋巴结转移或远处转移，这也成了治疗失败的主要原因。

对于复发或转移性鼻咽癌，目前的治疗手段有限，一线标准治疗方案是以铂类为基础的两药联合化疗，患者的生存情况亟待改善。对于一线含铂类化疗失败的患者，目前仍缺乏标准的后线治疗方案。

PD-1药物的出现，似乎给这类患者又带来了一线生机。多项研究发现，PD-1的表达与鼻咽癌的预后不良相关，说明PD-1类药物可以作为治疗鼻咽癌的一种潜在治疗选择。

那么PD-1究竟能否治疗鼻咽癌，让患者的生命延长呢？我们对已在我国上市的几种PD-1治疗鼻咽癌的研究进行了一个梳理。

特瑞普利单抗

特瑞普利单抗是由君实生物自主研发的抗PD-1单抗药物。

2020年9月，特瑞普利单抗用于复发或转移性鼻咽癌含铂治疗后的二线及以上治疗获得FDA突破性疗法认定。

2021年2月，特瑞普利单抗用于既往接受过二线及以上系统治疗失败的复发/转移性鼻咽癌患者的治疗获得中国国家药品监督管理局（NMPA）批准上市，成为全球首个获批用于治疗鼻咽癌的免疫检查点抑制剂。

2021年3月，基于早前的突破性疗法认定，君实生物开始向FDA滚动提交特瑞普利单抗治疗复发或转移性鼻咽癌的BLA并获得滚动审评，成为首个向FDA提交BLA的国产抗PD-1单抗。

2021年8月，特瑞普利单抗联合吉西他滨/顺铂作为晚期复发或转移性鼻咽癌患者的一线治疗获得FDA突破性疗法认定，进一步拓宽了FDA对特瑞普利单抗治疗鼻咽癌适应症的认定范围。

卡瑞利珠单抗

卡瑞利珠单抗（camrelizumab，艾瑞卡®），是一款由恒瑞医药自主研发的国产PD-1抑制剂。该药于2021年4月获得NMPA批准用于既往接受过二线及以上化疗后疾病进展或不可耐受的晚期鼻咽癌（NPC）患者的治疗。同年6月，卡瑞利珠单抗又获NMPA批准联合顺铂和吉西他滨用于局部复发或转移性鼻咽癌患者的一线治疗。

帕博利珠单抗

帕博利珠单抗（pembrolizumab，商品名Keytruda），简称K药，2014年9月FDA批准帕博利珠单抗用于治疗晚期或不可切除的恶性黑色素瘤，于2016年进入中国市场。

纳武利尤单抗

纳武利尤单抗（Nivolumab，商品名：欧狄沃/Opdivo），简称O药。自2014年在日本首次获批上市以来，纳武利尤单抗已在全球60多个国家及地区被批准用于治疗包括鼻咽癌在内的各种类型的癌症，并且正在进行大量临床试验。

除了上面提到的几种PD-1抑制剂，还有一些其他的PD-1也在探索治疗鼻咽癌的道路上，比如神州百济的替雷利珠单抗（tislelizumab），诺华的斯巴达珠单抗（Spartalizumab，PDR001），罗氏阿替利珠单抗（Atezolizumab）等等。

从目前发表的文献来看，使用PD-1抑制剂对治疗鼻咽癌有一定的临床疗效。基于前期的临床研究和对晚期或转移鼻咽癌治疗的迫切需求，目前已有两种国产PD-1在我国获批上市用于鼻咽癌的治疗，但在FDA尚无治疗鼻咽癌的PD-1类药物获批。

未来，我们需要更多的临床数据来支持PD-1抑制剂对鼻咽癌的疗效。不过，PD-1免疫疗法也为鼻咽癌的治疗带来了一种新的可能， 一旦有更多数据证明其疗效，无疑是对鼻咽癌患者特别是晚期患者的一个好消息。

文中文献检索筛选结果由EBM AI-Reviewer文献筛选系统支持完成。

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