Sonidegib (Odomzo) for the Systemic Treatment of Adults With Recurrent, Locally Advanced Basal Cell Skin Cancer.
Sonidegib (Odomzo) for the Systemic Treatment of Adults With Recurrent, Locally Advanced Basal Cell Skin Cancer.
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Sonidegib (Odomzo) 用于系统治疗成人复发性局部晚期基底细胞皮肤癌。
DOI：
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
L. Corry
中科院分区：
文献类型：
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作者：
Troy D Kish;L. Corry
非黑色素瘤皮肤癌(NMSC)是美国最常见的恶性肿瘤，每年诊断病例超过540万例。1 NMSC分为基底细胞癌(BCC)和鳞状细胞癌(SCC)，基底细胞癌的发病率是鳞状细胞癌的四到五倍。BCC的标准一线治疗通常涉及局部手术，如刮宫、电切、手术切除或放射治疗。2在最新数据(2011年以来)中，美国用于癌症治疗的医疗总支出估计超过880亿美元，其中包括NMSC.3，4虽然治疗NMSC的成本可能只占癌症治疗总成本的一小部分，但必须考虑其他因素。例如，随着特定人群的扩大，基底细胞癌的发病率预计会增加，例如65岁以上的人、免疫抑制患者和以前接受过治疗的患者经历疾病复发；这可能会增加成本。
由于缺乏标准化的分期和报告要求，局部晚期基底细胞癌或转移性基底细胞癌的发生率难以估计，但据估计，局部晚期基底细胞癌发生在1%到10%的基底细胞癌患者中，发生在0.0028%到0.5%的基底细胞癌患者中。6局部晚期基底细胞癌患者的中位生存期为8个月。7直到最近，只有有限的治疗方案可供选择，如顺铂；然而，Hedgehog(HH)信号通路在肿瘤发生中发挥的关键作用的发现为新疗法的开发打开了大门，如vismodegib(Erivedge，Genentech)。
平滑蛋白(SMO)是一种跨膜蛋白，激活HH途径，导致胶质瘤相关癌基因转录因子(GLI1、GLI2和GLI3)的产生。这些因子是调节细胞分化、增殖和存活的途径的最终组成部分。
2015年7月，美国食品和药物管理局(FDA)批准SMO抑制剂sonidegib(Odomzo，Novartis)用于治疗手术或放射治疗后复发的成人LABCC，或那些不适合手术或放射治疗的患者。Sonidegeb的主要竞争对手是vismodegib，另一种SMO抑制剂，自2012年以来一直用于治疗不适合手术或放射治疗的LABCC患者和mBCC.13，14 vismodegib是FDA批准的第一种治疗晚期BCC.13的药物。
Non-melanoma skin cancer (NMSC) is the most common malignancy in the United States, with more than 5.4 million cases diagnosed annually.1 NMSC is categorized as either basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), with BCC occurring at a fourfold to fivefold higher rate than SCC. Standard first-line treatment of BCC usually involves local procedures, such as curettage, electrodessication, surgical excision, or radiation therapy.2 In the most recent data (from 2011), total health care expenditures for cancer treatments in the U.S. were estimated to exceed $88 billion, including $4.8 billion for NMSC.3,4 While the cost of treating NMSC may be a small fraction of the overall cost of cancer therapies, additional factors must be considered. For instance, the rate of BCC is expected to grow as specific populations expand, such as people older than 65 years of age, immunosuppressed patients, and previously treated patients experiencing disease recurrence; this may increase costs.5
Estimates of the rate of locally advanced BCC (laBCC) or metastatic BCC (mBCC) are elusive because of a lack of standardization in staging and reporting requirements, but it has been estimated that laBCC occurs in 1% to 10% of BCC patients, and that mBCC occurs in 0.0028% to 0.5% of BCC patients.6 Patients with mBCC have a median survival of eight months.7 Until recently, only limited treatment options, such as cisplatin, have been available for patients with laBCC or mBCC8; however, the discovery of the key role played by the hedgehog (Hh) signaling pathway in tumorigenesis has opened the door for the development of new therapies, such as vismodegib (Erivedge, Genentech).9
Smoothened (SMO), a transmembrane protein, activates the Hh pathway, leading to the production of glioma-associated oncogene transcription factors (GLI1, GLI2, and GLI3). These factors are the final component of the pathway that regulates cellular differentiation, proliferation, and survival.10
In July 2015, the Food and Drug Administration (FDA) approved the SMO inhibitor sonidegib (Odomzo, Novartis) for the treatment of adults with laBCC that has recurred after surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy.11,12 Sonidegeb’s key competitor is vismodegib, another SMO inhibitor, which has been used since 2012 to treat patients with laBCC who are not candidates for surgery or radiation and patients with mBCC.13,14 Vismodegib was the first FDA-approved drug for advanced BCC.13