美国食品和药物管理局批准摘要:托瓦法尼布用于复发性或耐火性BRAF改变的儿科低级质瘤
Sonia Singh1, Diana Bradford1, Somak Chatterjee1
1Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
概括
托瓦法尼布是针对患有复发性或耐药性儿科低度质瘤 (pLGG) 的儿童,这些儿童具有特定的BRAF变异的新疗法. 这种FDA批准的疗法在临床试验中显示出显著的反应率和持续时间.
科学领域:
- 儿科瘤学 儿科瘤学
- 分子向疗法分子向疗法
- 在RAF中,Kinase抑制作用.
背景情况:
- 儿科低度结质瘤 (pLGG) 是一个具有挑战性的诊断在年轻患者.
- 对于复发或耐火的pLGG与BRAF变化,存在有限的全身疗法选择.
- 托沃法尼布针对特定的BRAF融合,重新排列或V600突变.
研究的目的:
- 评估托沃法尼布在患有复发性或耐火性PLGG的患者中的疗效和安全性.
- 评估对托沃法尼布的整体反应率和反应持续时间.
- 为了支持FDA对该患者群体的托沃法尼布的加速批准.
主要方法:
- FIREFLY-1试验:一个单臂,开放标签,多中心研究.
- 招募了6个月至25岁的患者,患有复发性/耐药的PLGG和激活BRAF变异.
- 主要终点:通过盲目的独立中央审查进行放射性总体反应率.
主要成果:
- 在76名患者中,总体应答率为51% (95% CI,40-63).
- 响应的中位持续时间为13.8个月 (95% CI,11.3不可估计).
- 代表了FDA首次批准使用BRAF融合/重组的plLGG全身疗法.
结论:
- 托沃法尼布在治疗复发性或耐火性儿科低度质瘤与BRAF变化的治疗中表现出显著的疗效.
- 加快FDA批准为这个特定的患者群体提供了一个新的治疗选择.
- 目前正在进行的试验将进一步证实tovorafenib的长期益处.
相关概念视频
02:56Treatment Resistant Cancers
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
02:56Treatment Resistent Cancers
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
01:26FDA Approved Drugs: Changes to Approved Drugs
Post-approval, manufacturers may modify an approved new or generic drug product. Such modifications can encompass alterations in the Active Pharmaceutical Ingredient (API), manufacturing process, formulation, batch size, manufacturing site, and container closure system (FDA Guidance for Industry, April 2004). Often, a drug product may undergo multiple changes.These modifications require careful evaluation to determine their potential impact on the drug product's identity, strength, quality,...
01:23Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption
Understanding the physiological differences in the pediatric population is crucial for effective pharmacotherapy. Neonates, infants, and children exhibit significant variations in gastric pH, gastric emptying time, intestinal transit time, and biliary function. These variations profoundly affect oral drug absorption, necessitating a nuanced approach to pediatric dosing.Neonates present with a unique physiological profile, having a gastric pH greater than 4 and faster and more irregular gastric...