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话题:FDA批准Necitumumab用于转移性鳞型NSCLC

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张品良大夫

山东省肿瘤医院

呼吸内科

发表于:2015-12-08

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美国食品及药物管理局(FDA)已经批准necitumumab(Portrazza)联合吉西他滨与顺铂用于转移性鳞型非小细胞肺癌(NSCLC)患者的一线治疗。 

Necitumumab不适用于非鳞NSCLC的治疗。

Necitumumab是一种重组人IgG1单抗与人表皮生长因子受体(EGFR)结合然后阻滞表皮生长因子受体与其配体结合。山东省肿瘤防治研究院肿瘤内科张品良

批准是基于一项1093例转移性鳞型非小细胞肺癌既往未曾接受过针对转移灶治疗的患者的研究。 

患者随机接受necitumumab 800毫克(第1、8天)加吉西他滨1250mg/㎡(第1、8天)和顺铂75mg/㎡(第1天,每3周为1周期;n=545)或只有吉西他滨与顺铂(n=548)。

主要终点是总生存。 

也评估无进展生存(PFS)和总有效率(ORR)。

Necitumumab组患者中位总生存期是11.5个月而只有吉西他滨与顺铂者9.9个月(风险比[HR]=0.84;P =.01)。

分配至三联治疗的患者中位无进展生存期是5.7个月而分配至只有吉西他滨与顺铂者是5.5个月(HR =0.85;P =.02)。

组间客观反应率没有观察到差异necitumumab组总有效率31%而双药治疗组29%。

一项随机、标签开放、多中心试验确定necitumumab联合培美曲塞和顺铂(PC)用于治疗转移性非鳞非小细胞肺癌患者缺乏疗效。 

既往未曾针对转移灶化疗的患者被随机化(1∶1)至接受necitumumab加培美曲塞和顺铂或只有培美曲塞和顺铂。 

在necitumumab组由于增加全因及血栓栓塞事件死亡率,在入组633例患者后本研究被提前关闭。 

Necitumumab加入到培美曲塞和顺铂没有改善总生存期(HR=1.01 P =.96)、无进展生存期(HR=0.96)或总有效率(31%对32%)。

观察到最常见的不良反应(所有等级)是皮疹和低镁血症,necitumumab治疗的患者≥30%而只有吉西他滨与顺铂组≥2%。 

严重且临床上值得注意的不良事件包括低镁血症、静脉与动脉血栓栓塞事件、皮肤毒性、输液反应,并且在非鳞非小细胞肺癌患者中增加毒性与死亡率。

Necitumumab组中3%的患者记录了心血管事件死亡或猝死。 

在给予necitumumab期间及以后医护人员应密切监测血清电解质,包括血清镁、钾和钙。 

对于3或4度电解质异常不给necitumumab。

专业医护人员应该通过在线http://www.FDA.gov/medwatch/report.htm、传真(1-800-FDA-0178)或在线提供的邮资已付地址邮寄或打电话(1-800-FDA-1088)的形式向食品及药物管理局医疗观察报告系统呈报所有可疑与任何药物与设备使用有关的严重不良事件。

信源:美国食品和药物管理局

FDA Approves Necitumumab for Metastatic Squamous NSCLC

ROCKVILLE, Md

November 24, 2015

The US Food and Drug Administration (FDA) has approved necitumumab (Portrazza), in combination with gemcitabine and cisplatin, for first-line treatment of patients with metastatic squamous non-small-cell lung cancer (NSCLC). 

Necitumumab is not indicated for treatment of non-squamous NSCLC.

Necitumumab is a recombinant human IgG1 monoclonal antibody that binds to the human epidermal growth factor receptor (EGFR) and blocks the binding of EGFR to its ligands.

Approval was based on a study of 1,093 patients with metastatic squamous NSCLC who had not received prior therapy for metastatic disease. 

Patients were randomised to receive necitumumab 800 mg (days 1 and 8) plus gemcitabine 1,250 mg/m2 (days 1 and 8) and cisplatin 75mg/m2 (day 1 of each 3-week cycle; n = 545) or gemcitabine and cisplatin alone (n = 548).

The primary endpoint was overall survival. Progression-free survival (PFS) and overall response rate (ORR) were also assessed.

Median OS was 11.5 months for patients in the necitumumab group compared with 9.9 months for those assigned to gemcitabine and cisplatin alone (hazard ratio [HR] = 0.84; P = .01).

Median PFS was 5.7 months for patients assigned to the triple combination therapy versus 5.5 months for those assigned to gemcitabine and cisplatin alone (HR = 0.85; P = .02).

No difference in ORR between arms was observed with an ORR of 31% for the necitumumab group and 29% for the dual therapy group.

Lack of efficacy of necitumumab in combination with pemetrexed and cisplatin (PC) for the treatment of patients with metastatic non-squamous NSCLC was determined in a randomised, open-label, multicentre trial. 

Patients with no prior chemotherapy for metastatic disease were randomised (1:1) to receive necitumumab plus PC or PC alone. 

The study was closed prematurely after 633 patients were enrolled due to increased incidence of death due to any cause and of thromboembolic events in the necitumumab arm. Addition of necitumumab to PC did not improve OS (HR = 1.01P = .96), PFS (HR = 0.96), or ORR (31% vs 32%).

The most common adverse reactions (all grades) observed in necitumumab-treated patients at a rate of ≥30% and ≥2% than the gemcitabine and cisplatin alone arm were rash and hypomagnesemia. 

Serious and clinically significant adverse events included hypomagnesemia, venous and arterial thromboembolic events, dermatologic toxicities, infusion reactions, and increased toxicity and increased mortality in patients with non-squamous NSCLC.

Death attributed to cardiovascular events or sudden death was reported in 3% of the patients in the necitumumab group. 

Health care providers should closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after necitumumab administration. Withhold necitumumab for grade 3 or 4 electrolyte abnormalities.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).


SOURCE: US Food and Drug Administration


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