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新药Kisqali(ribociclib 以前名 LEE011)片获FDA批准 一线治疗HR+/HER2-晚期或转移性乳腺癌
近日，由诺华（Novartis）研发的新型口服靶向抗癌药Kisqali（ribociclib，前称LEE011）获美国FDA批准上市，联合芳香酶抑制剂，作为一种初始内分泌疗法，用于绝经后女性激素受体阳性/人类表皮生长因子受体2阴性（HR+/HER2-）晚期或转移性乳腺癌的一线治疗
批准日期：2017年3月13日;公司：诺华制药公司
KISQALI(ribociclib，以前名 LEE011)片，为口服使用
美国初次批准：2017
作用机制
Ribociclib是一种周期素-依赖性激酶(CDK)4和6的抑制剂。这些激酶与D-周期素结合被活化和在信号途径中起至关重要作用，它导致细胞周期进展和细胞增殖。通过视网膜母细胞瘤蛋白质[retinoblastoma protein](pRb)的磷酸化，周期素D-CDK4/6复合物调节细胞周期进展。
在体外，ribociclib在乳癌细胞系中减低pRb磷酸化导致细胞周期停止在细胞周期的G1期和减低细胞增殖，在体内，在大鼠一种异种移植模型用单药ribociclib治疗人肿瘤细胞导致肿瘤体积减低，它与pRb磷酸化抑制作用相关。在研究利用患者-衍生的雌激素受体阳性乳癌异种移植模型，ribociclib和抗雌激素(如来曲唑)的联用与各药单独比较导致在肿瘤生长抑制作用增加。
适应证和用途
KISQALI是一种激酶抑制剂适用与一个芳香化酶抑制剂组合作为初始基于内分泌治疗为有激素受体(HR)-阳性，人表皮生长因子受体2(HER2)-阴性晚期或转移乳癌绝经后妇女的治疗。
剂量和给药方法
KISQALI片被口服有或无食物与来曲唑[letrozole]联用.
● 推荐的开始剂量：600mg口服(三200mg片)服用每天1次有或无食物共21连续天接着7天不用治疗。
● 根据个体安全性和耐受性可能需要剂量中断，减低。和/或终止。
剂型和规格
●片：200mg
禁忌证
无。
警告和注意事项
● QT间期延长：用KISQALI治疗开始前监视心电图(ECGs)和电解质。在第一个疗程约天14重和当临床上有适应证时。
● 肝胆毒性：曽观察到在血清转氨酶水平中增加。开始用KISQALI治疗前，进行肝功能测试(LFTs)。对头2个疗程监视LFTs每2周，在随后4个疗程每个开始时，和当临床上有适应证时。
● 中性细胞减少：开始用KISQALI治疗时进行完全血细胞计数(CBC)。对头2个疗程每2周监视CBC，和当临床上有适应证时。
● 胚胎-胎儿毒性：可致胎儿危害。忠告患者对胎儿潜在风险和治疗期间使用有效避孕。
不良反应
最常见不良反应(发生率≥20%)为中性细胞减少，恶心，疲乏，腹泻，白细胞减少，脱发，呕吐，便秘，头痛和背痛。
药物相互作用
● CYP3A4抑制剂：避免KISQALI与强CYP3A抑制剂同时使用。如强抑制剂不能避免，减低KISQALI剂量
● CYP3A4诱导剂：避免KISQALI与强CYP3A诱导剂的同时使用.
● CYP3A底物：当与KISQALI同时给予时，有狭窄治疗指数敏感的CYP3A底物的剂量可能需要减低。
● 已知延长QT间期药物：避免同时使用已知延长QT间期例如抗-心律失常药物。
在特殊人群中使用
哺乳：建议不哺乳喂养。
包装规格[注：以下产品是单剂和组合剂，不同规格和不同价格均可拿到货，采购以在线咨询为准]
Kisqali TAB
KISQALI 200MG DAILY TAB 1X21 BLST 21/EA RIBOCICLIB 00078-0860-01
KISQALI 400MG DAILY TAB 3X14 BLST 42/EA RIBOCICLIB 00078-0867-42
KISQALI 600MG DAILY TAB 3X21 BLST 63/EA RIBOCICLIB 00078-0874-63
Kisqali FeMara Co-Pack组合药
KISQALI/FEMARA 200MG TAB 1X21 BLST 49/EA RIBOCICLIB/LETROZOLE 00078-0909-61
KISQALI/FEMARA 400MG TAB 3X14 BLST 70/EA RIBOCICLIB/LETROZOLE 00078-0916-61
KISQALI/FEMARA 600MG TAB 3X21 BLST 91/EA RIBOCICLIB/LETROZOLE 00078-0923-61
完整说明书附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aaeaef94-f3f5-4367-8ea2-b181d7be2da8
以下是组合剂部份资料附：
Kisqali Femara Co-Pack：Combination pack for two cancer drugs approved
FDA has approved a combination package containing two prescription drugs for advanced breast cancer. Novartis reports that FDA has approved the Kisqali Femara Co-Pack, calling it the "first and only" currently available combination pack with two prescription products for advanced breast cancer: ribociclib tablets and letrozole tablets.
According to a news release issued by Novartis, Kisqali was approved on March 13, 2017, in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer. Femara is an aromatase inhibitor approved for first-line treatment of postmenopausal women with HR+ or unknown advanced breast cancer; it has been available for nearly 20 years, and research by Novartis has continued during this time, it was reported.
A spokesperson tells PMP News that Novartis is doing the packaging internally. The combination package contains a 28-day cycle of the two medicines. It can be obtained with one prescription and with one copay, making the Kisqali Femara Co-Pack available at the same cost as Kisqali alone, according to the release. It is available in three dosage strengths: Kisqali 600 mg plus Femara 2.5 mg, Kisqali 400 mg plus Femara 2.5 mg, and Kisqali 200 mg plus Femara 2.5 mg.
“As we strive to keep the patient at the center of every decision that we make at Novartis, we are pleased that collaborating closely with the FDA has resulted in our being able to offer this unique combination pack of two prescription cancer medicines,” stated Bill Hinshaw, Executive Vice President and Head, US, Novartis Oncology, in the release. “Providing physicians a convenient one package prescribing option for their patients underscores our commitment to deliver innovative treatment solutions to the metastatic breast cancer community.”
The Kisqali Femara Co-Pack will be available in the United States later this month at both specialty and retail pharmacies. | 
