China’s National Medical Products Administration (NMPA) has approved zorifertinib hydrochloride tablets (Zorifer; formerly AZD3759) for the first-line treatment of adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletion or exon 21 L858R substitution mutations and central nervous system (CNS) metastases.

中国国家医药产品管理局（NMPA）已批准盐酸佐利非替尼片（Zorifer；原名AZD3759）用于一线治疗患有EGFR外显子19缺失或外显子21 L858R替代突变和中枢神经系统（CNS）转移的局部晚期或转移性非小细胞肺癌（NSCLC）的成年患者。

Zorifertinib is currently the only available EGFR TKI specifically designed as a as non–blood-brain barrier efflux protein substrate that can fully penetrate the blood-brain barrier. The agent’s therapeutic advantages, including its ability to control intracranial lesions and prolong progression-free survival (PFS), were demonstrated in the phase III EVEREST trial (NCT03653546)...

Zorifertinib是目前唯一可用的EGFR TKI，专门设计为可以完全穿透血脑屏障的as非血脑屏障外排蛋白底物。该药物的治疗优势，包括其控制颅内病变和延长无进展生存期（PFS）的能力，已在III期EVEREST试验（NCT03653546）中得到证实。。。

In the phase III EVEREST trial (NCT03653546). Zorifertinib significantly reduced the risk of intracranial progression or death by 37% (P = .0018) vs a first-generation EGFR TKI and generated an intracranial PFS of 17.9 months. Consistent and significant benefits with zorifertinib were observed across patient subgroups, including those with intracranial symptoms, EGFR L858R mutations, and more than 3 intracranial lesions..

在III期珠穆朗玛峰试验（NCT03653546）中。与第一代EGFR TKI相比，佐利非替尼显着降低了颅内进展或死亡的风险37%（P=0.0018），并产生了17.9个月的颅内PFS。在患者亚组中观察到佐利非替尼具有一致且显着的益处，包括那些有颅内症状，EGFR L858R突变和3个以上颅内病变的患者。。

Additional results from EVEREST published in Med by CellPress in October 2024 showed that the median PFS with zorifertinib (n = 220) was 9.6 months vs 6.9 months with the control (n = 219; HR, 0.719; 95% CI, 0.580-0.893; P = .0024). Although overall survival (OS) data were immature at the time of analysis, a trend toward improved OS was observed among patients subsequently treated with third-generation TKI.

2024年10月CellPress在Med上发表的珠穆朗玛峰的其他结果显示，佐利非替尼（n=220）的中位PFS为9.6个月，而对照组为6.9个月（n=219；HR，0.719；95%CI，0.580-0.893；P=0.0024）。。

In this patient subgroup, the estimated median OS was 37.3 months with zorifertinib vs 31.8 months with the control (HR, 0.833; 95% CI, 0.524-1.283). Regarding safety, the agent displayed a safety profile consistent with reported data..

在该患者亚组中，佐利非替尼的估计中位OS为37.3个月，而对照组为31.8个月（HR为0.833；95%CI为0.524-1.283）。关于安全性，该代理显示了与报告数据一致的安全概况。。

In a news release, Yi-Long Wu, FACS, of Guangdong Provincial People’s Hospital in China, emphasized the lack of clinical head-to-head randomized trials addressing drug therapy for lung cancer with CNS metastases, despite the approval of multiple agents for EGFR-mutated NSCLC. Yilong, who is also the global lead principal investigator for the EVEREST study, added that these findings suggest that combining or sequencing zorifertinib with third-generation TKIs may lead to improved prognoses..

在一份新闻稿中，中国广东省人民医院FACS的吴义龙强调，尽管批准了多种EGFR突变NSCLC药物，但缺乏针对中枢神经系统转移肺癌药物治疗的临床头对头随机试验。伊龙（Yilong）也是珠穆朗玛峰研究的全球首席首席研究员，他补充说，这些发现表明，将佐利非替尼与第三代TKI联合或测序可能会改善预后。。

EVEREST is the world’s first large-scale, registered, international, multi-center, randomized controlled study evaluating zorifertinib in patients with advanced NSCLC and CNS metastases. The study enrolled patients with EGFR-sensitizing mutations, treatment-naive NSCLC, and at least 1 non-irradiated symptomatic or asymptomatic CNS metastasis.

珠穆朗玛峰是世界上第一个大规模，注册，国际，多中心，随机对照研究，评估佐利非替尼治疗晚期非小细胞肺癌和中枢神经系统转移患者。该研究招募了EGFR致敏突变，未接受治疗的NSCLC和至少1例未经照射的有症状或无症状中枢神经系统转移的患者。

Documented MRI-confirmed CNS metastasis, no prior brain radiotherapy, no EGFR T790M, KRAS or cMET mutations, and an ECOG performance status of 0 or 1 was required. The study was conducted at 58 sites across mainland China, South Korea, Taiwan, and Singapore. Study enrollment began on February 1, 2019, and concluded on January 12, 2021.

有记录的MRI证实中枢神经系统转移，没有先前的脑放疗，没有EGFR T790M，KRAS或cMET突变，并且需要ECOG表现状态为0或1。这项研究在中国大陆、韩国、台湾和新加坡的58个地点进行。研究入学于2019年2月1日开始，2021年1月12日结束。

Upon enrollment, 439 patients were randomly assigned 1:1 to either 200 mg of zorifertinib twice-daily or a first-generation EGFR-TKI; the latter treatment included 250 mg of gefitinib (Iressa) or 150 mg of erlotinib (Tarceva) daily..

入组后，439名患者被随机分配1:1至200 mg佐利非替尼，每日两次或第一代EGFR-TKI；后一种治疗包括每天250毫克吉非替尼（易瑞沙）或150毫克厄洛替尼（塔尔切娃）。。

Citation:  WZhou Q, Yu Y, Xing L, et al. 'First-line zorifertinib for EGFR-mutant non-small cell lung cancer with central nervous system metastases: The phase III EVEREST trial'. Med. Published online October 3, 2024. doi:10.1016/j.medj.2024.09.002.

引用：WZhou Q，Yu Y，Xing L等，“用于EGFR突变型非小细胞肺癌伴中枢神经系统转移的一线佐利非替尼：III期EVEREST试验”。医学杂志于2024年10月3日在线发布。doi:10.1016/j.medj.2024.09.002。

Condition: NSCLC + Brain Metastases

Type: drug

类型：药物