新型抗血管生成药物获准治疗部分转移性结直肠癌

圣路易斯(MD Consult)——2012年8月3日，赛诺菲公司和Regeneron制药公司宣布，美国食品药品管理局(FDA)已经批准注射用Zaltrap(ziv-aflibercept)与5-氟尿嘧啶、亚叶酸及伊立替康(FOLFIRI)联用，治疗对含奥沙利铂治疗方案耐药或在完成该方案治疗后病情进展的转移性结直肠癌(mCRC)患者。Zaltrap是一种血管生成抑制剂。

FDA批准Zaltrap是基于一项3期、随机、国际、双盲临床试验的数据，该试验在mCRC患者中将FOLFIRI+Zaltrap治疗与FOLFIRI+安慰剂进行了比较，受试群体为1,226例先前曾接受含奥沙利铂方案治疗的mCRC患者，这些患者在研究中接受了随机化分组，其中有28%的患者之前曾接受贝伐珠单抗治疗。

在FOLFIRI治疗的基础上又接受Zaltrap治疗的患者生存期显著延长，从12.06个月延长至13.5个月，相对风险降低18%；另外，无进展生存期也显著延长，从4.67个月延长至6.9个月；Zaltrap+FOLFIRI治疗组的总应答率为19.8%，而FOLFIRI+安慰剂组为11.1%(P=0.0001)。

Zaltrap+FOLFIRI治疗组最常见的不良反应(发生率均≥20%)按发生率从高到低的顺序依次为白细胞减少、腹泻、中性粒细胞减少、蛋白尿、天冬氨酸氨基转移酶水平升高、胃炎、疲乏、血小板减少、丙氨酸氨基转移酶水平升高、高血压、体重减少、食欲下降、鼻衄、腹痛、发声困难、血清肌酐水平升高及头痛。

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ST LOUIS (MD Consult) - On August 3, 2012, Sanofi and Regeneron Pharmaceuticals announced that the US Food and Drug Administration (FDA) has approved Zaltrap (ziv-aflibercept) for injection, in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) for the treatment of patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed after completion of an oxaliplatin-containing regimen. Zaltrap is an angiogenesis inhibitor.

The Zaltrap approval was granted on the basis of data from a phase 3, randomized, multinational, double-blind trial that compared the use of FOLFIRI in combination with either Zaltrap or placebo in patients with mCRC. The 1226 patients with mCRC who underwent randomization in the study had previously been treated with an oxaliplatin-containing regimen. Twenty-eight percent of patients had received prior bevacizumab therapy.

Patients in the study who received Zaltrap in addition to FOLFIRI experienced significantly improved survival from 12.06 months to 13.5 months, an 18% releative risk reduction. A significant improval in progression-free survival from 4.67 months to 6.9 months was also observed. The overall response rate in the Zaltrap plus FOLFIRI arm was 19.8% versus 11.1% for the FOLFIRI plus placebo arm (P = .0001).

The most common adverse reactions (all grades ≥ 20% incidence) at higher incidence in the Zaltrap/FOLFIRI arm, in order of decreasing frequency, were leukopenia, diarrhea, neutropenia, proteinuria, increased aspartate aminotransferase levels, stomatitis, fatigue, thrombocytopenia, increased alanine aminotransferase levels, hypertension, decreased weight, decreased appetite, epistaxis, abdominal pain, dysphonia, increased serum creatinine levels, and headache.