美国FDA7月12日批准阿法替尼上市一线治疗EGFR突变的晚期NSCLC病人

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FDA Approves Gilotrif
http://www.drugs.com/newdrugs/fd ... ng-cancer-3851.html
July 12, 2013 -- The U.S. Food and Drug Administration today approved Gilotrif (afatinib) for patients with late stage (metastatic) non-small cell lung cancer (NSCLC) whose tumors express specific types of epidermal growth factor receptor (EGFR) gene mutations, as detected by an FDA-approved test.
Gilotrif is a tyrosine kinase inhibitor that blocks proteins that promote the development of cancerous cells. It is intended for patients whose tumors express the EGFR exon 19 deletions or exon 21 L858R substitution gene mutations. Gilotrif is being approved concurrently with the therascreen EGFR RGQ PCR Kit, a companion diagnostic that helps determine if a patient’s lung cancer cells express the EGFR mutations.

“Today’s approvals further illustrate how a greater understanding of the underlying molecular pathways of a disease can lead to the development of targeted treatments,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Gilotrif is the second drug approved this year for patients with untreated metastatic NSCLC whose tumors have the EGFR exon 19 deletions or exon 21 L858R substitution mutations.”

In May, the FDA approved Tarceva (erlotinib) for first-line treatment of patients with NSCLC. Tarceva’s new indication was approved concurrently with the cobas EGFR Mutation Test, a companion diagnostic to identify patients with tumors having the EGFR gene mutations.

“The approval of companion diagnostic tests and drugs are important developments in oncology, as they help us bring safe and effective treatments to patients who need them,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health.

The FDA’s approval of the therascreen EGFR RGQ PCR Kit is based on data from the clinical study used to support Gilotrif’s approval. Tumor samples from NSCLC participants in the clinical trial helped to validate the test’s use for detecting EGFR mutations in this patient population.

Gilotrif’s safety and effectiveness were established in a clinical study of 345 participants with metastatic NSCLC whose tumors harbored EGFR mutations. Participants were randomly assigned to receive Gilotrif or up to six cycles of the chemotherapy drugs pemetrexed and cisplatin.

Participants receiving Gilotrif had a delay in tumor growth (progression-free survival) that was 4.2 months later than those receiving chemotherapy. There was no statistically significant difference in overall survival.

Common side effects of Gilotrif include diarrhea, skin breakouts that resemble acne, dry skin, itching (pruritus), inflammation of the mouth, skin infection around the nails (paronychia), decreased appetite, decreased weight, inflammation of the bladder (cystitis), nose bleed, runny nose, fever, eye inflammation and low potassium levels in the blood (hypokalemia). Serious side effects include diarrhea that can result in kidney failure and severe dehydration, severe rash, lung inflammation and liver toxicity.

The FDA reviewed Gilotrif under its priority review program, which provides an expedited review for drugs that may provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to marketed products.

Gilotrif is marketed by Ridgefield, Conn.-based Boehringer Ingelheim Pharmaceuticals, Inc. The therascreen EGFR RGQ PCR Kit is manufactured by QIAGEN Manchester Ltd., based in the United Kingdom. The cobas EGFR Mutation Test is manufactured by the Roche Molecular Systems in Pleasanton, Calif., and Tarceva is co-marketed by California-based Genentech, a member of the Roche Group, and OSI Pharmaceuticals of Farmingdale, N.Y.

老马 · 发表于 2013-7-13 18:42:23

几点相关说明：
1.适应对象为晚期非小细胞肺癌病人，并具有EGFR基因突变（18,19,21）。
2.上市剂型为40mg,30mg,20mg，相当于（59.12 mg, 44.34 mg, 29.56 mg 阿法替尼双马来酸盐）。
3. 需要引起注意的严重副作用：
（1）胚胎胎儿毒性，孕妇需要停药。
（2）严重的腹泻，可能会引起脱水和肾功能衰竭，如果控制不住腹泻，需要停药。
（3）严重的皮肤毒性：0.15%的病人可能会发生大疱和剥脱皮肤疾病，需要停药。
（4）1.5%的病人可能会发生间质性肺炎（ILD），需要停药。
（5）0.18%的病人可能会发生致命的肝毒性，需要停药。
（6）0.8%的病人可能会发生严重的角膜炎，需要停药。
避免共用的药物：
（1）P-glycoprotein (P-gp)抑制剂，比如蛋白酶抑制剂Ritonavir(利托那韦)，在阿法替尼前1小时服用，则阿法替尼的血药浓度将增加48%。在阿法替尼后6小时服用，则无影响。
其它P-gp抑制剂(cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone)
（2）P-glycoprotein (P-gp)诱导剂，比如Rifampicin（利福平），600mg每天，同时服用7天，则阿法替尼的血药浓度将降低34%。
其它P-gp诱导剂（carbamazepine, phenytoin, phenobarbital, and St. John’s wort）
阿法替尼服用2-5小时后达到血药峰值，半衰期为37小时，8天后到稳态血药浓度，达到2.8倍AUC和2.1倍Cmax。阿法替尼不是CYP450抑制剂或者诱导剂。

Gilotrif（阿法替尼，Bibw 2992）说明书.PDF (551.21 KB, 下载次数: 101)