2015年2月3日,美国食品和药品监管局(FDA)授权加速批准Ibrance(palbociclib)治疗晚期(转移)乳癌。
在美国乳癌是在妇女中第二位最常见类型癌症。它在乳腺组织中形成和在晚期病例，播散至周围正常组织。美国癌症研究所估计2014年232,670例美国妇女被诊断有乳癌和40,000例死于此病。
Ibrance通过涉及促进癌细胞的生长抑制性分子，被称为周期蛋白依赖性激酶(CDKs)4和6起作用。Ibrance是意向为有雌激素受体(ER)-阳性，人表皮生长因子受体2(HER2)-阴性转移乳癌，未曾接受某种基于内分泌治疗绝经后妇女。它还与来曲唑[letrozole]联用，另一个FDA-批准的产品在绝经后妇女中用于治疗某些类型乳癌.
FDA 药品评价和研究中心血液学和肿瘤产品室主任Richard Pazdur医学博士说：“palbociclib添加至来曲唑对被诊断有转移乳癌妇女提供一种新颖治疗选择，”“FDA承诺通过我们的加快批准监管加快癌症药物的上市批准。”
FDA授权Ibrance突破性治疗指定因为承办单位通过初步临床证据证实该药可提供超过可得到治疗实质性改善。它还接到优先审评，提供对意向提供某种严重情况治疗安全性和有效性的显著改善或满足未被满足医疗需求药物的加快审评。Ibrance正在比处方药用户收费目标日期2015年4月13日提前2个月被批准，这个日期是监管局计划完成这项申请审评的日期。
Ibrance正在FDA的加快批准程序下被批准，这个程序根据临床数据显示药物对某个合理地可能预测对患者获益的替代性终点有影响，允许批准某个治疗某种严重或危及生命疾病药物。这个程序提供患者更早得到鼓舞人有前途新药，而公司进行验证性临床试验。
在165例有ER-阳性，HER2-阴性晚期乳癌，对晚期疾病未曾接受既往治疗的绝经后妇女证实药物的疗效。临床研究参加者被随机赋予接受Ibrance与来曲唑或单独来曲唑。用Ibrance加来曲唑治疗的参加者生存约20.2个月无其疾病进展(无进展生存)，与之比较只接受来曲唑参加者见到约10.2个月。在此时不能得到总生存信息。
最常见药物副作用是感染斗争白细胞称为嗜中性减低(中性粒细胞减少)，白细胞减少，疲乏，地红细胞计数(贫血)，上呼吸道感染，恶心，口腔壁炎症(口炎)，脱发，腹泻，血小板减少，食欲减退，呕吐，和乏力，周围神经病变和鼻衄。卫生保健专业人员应告知患者这些风险。
建议开始治疗用125 mg剂量共21天，接着7天无治疗。卫生保健专业人员被忠告在治疗开始前和在每个疗程开始时，以及在头两个疗程第14天时和当临床指示时监视完全血细胞计数。
Ibrance是由总部在纽约的辉瑞公司上市。
IBRANCE® (palbociclib)approved for advanced breast cancer
4, 2015 /PRNewswire/ — Diplomat Pharmacy, Inc. (NYSE: DPLO), the nation’s largest independent specialty pharmacy, announced today it will dispense Pfizer’s new breakthrough medication, IBRANCE(®)(palbociclib), starting tomorrow, Feb. 5. IBRANCE(®) received approval from the Food and Drug Administration yesterday for use, when paired with letrozole, to treat metastasized tumors in postmenopausal women with a specific form of breast cancer.
http://photos.prnewswire.com/prnvar/20140928/148820
The approval for IBRANCE(®) came more than two months ahead of schedule, through the FDA’s Breakthrough Therapy designation and Priority Review programs. According to Pfizer, the registration trial showed that, compared to letrozole alone, IBRANCE(®) in combination with letrozole nearly doubled the time before tumors progressed. The drug is the first in a new class of anti-cancer agents, CDK 4/6 inhibitors, to be FDA-approved.
“IBRANCE(®) offers hope for the breast cancer community, and we’re excited to be able to offer it at Diplomat,” said Gary Kadlec, president of the company. “Patients facing metastatic breast cancer need the support of advancements like these, and we are honored to complement this treatment with focused care.”
IBRANCE(®) is indicated for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease.
www.diplomat.is.
New Drugs Online Report for palbociclib
Information
Generic Name: palbociclib
Trade Name: Ibrance
Synonym: PD-0332991
Entry Type: New molecular entity
Development and Regulatory status
UK: Phase III Clinical Trials
EU: Phase III Clinical Trials
US: Approved (Licensed)
UK launch Plans: Available only to registered users
Actual UK launch date:
Comments
Feb 15: US FDA grants approval of palbociclib (Ibrance) in postmenopausal women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer who have not received an endocrine-based therapy [13].
05/02/2015 08:41:08
Oct 14: Granted priority review by the FDA. The PDUFA date for palbociclib is April 13 2015 [11].
13/10/2014 17:31:20
Aug 14: Filed for marketing approval in the US in combination with letrozole, for the treatment of postmenopausal women with ER+, HER2- advanced breast cancer who have not received previous systemic treatment for their advanced disease. The submission is based on the final results of the PII PALOMA-1 trial comparing palbociclib plus letrozole vs letrozole alone in this population of patients [10].
19/08/2014 21:06:43
May 14: Pfizer will submit a New Drug Application with the US FDA later in 2014 for palbociclib, in combination with letrozole, for the first-line treatment of post-menopausal women with ER+, HER2- locally advanced or metastatic breast cancer, based on results from the PALOMA-1 study [9].
20/05/2014 10:54:13
Feb 14: Pfizer is likely to explore the possibility of filing in the US based on PII PALOMA-1 data via accelerated approval [7]
09/02/2014 18:39:20
Aug 13: Expected US launch 2015 [5].
28/08/2013 09:50:53
Apr 13: FDA grants palbociclib ´breakthrough´ drug status [4].
11/04/2013 09:49:05
Jan 13: Pfizer considering submitting for early approval based on PII results that showed the drug stopped disease progression for >2 years in 165 patients [1]
15/01/2013 14:49:11
Trial or other data
Dec 14: Results of the phase II PALOMA-1/TRIO-18 study have been published in the Lancet. The addition of palbociclib to letrozole (L) improved progression-free survival in postmenopausal women with advanced oestrogen receptor+ve and HER2-ve breast cancer (median 20.2 v 10.2 months with L alone; HR 0•488, 95% CI 0•319–0•748; p=0.0004). [12]
18/12/2014 10:39:47
Apr 14: Detailed results reported from the PII PALOMA-1 study. PALOMA-1 achieved its primary endpoint by significantly prolonging PFS in post-menopausal women with ER+, HER2- locally advanced or metastatic breast cancer (median PFS 20.2 months for palbociclib + letrozole vs 10.2 months for letrozole alone (HR=0.488 [95% CI: 0.319, 0.748]; p=0.0004). Secondary endpoints of duration of treatment and clinical benefit rate demonstrated superiority in combination arm. In an initial assessment of overall survival, a secondary endpoint, median OS was 37.5 vs 33.3 months in favour of the combination, a difference of 4.2 months (HR = 0.813, 95% CI: 0.492, 1.345). This OS observation at the time of final PFS analysis was not statistically significant. A follow-up OS analysis will be conducted following the accrual of additional events [8].
07/04/2014 10:56:03
NCT01740427 = PALOMA-2 (Study 1008)
09/02/2014 18:39:46
Feb 14: PALOMA-1 (also known as Study 1003) is a Phase 2 trial designed to assess the Progression Free Survival (PFS) of palbociclib (125 mg OD for three out of four weeks in repeated cycles) in combination with letrozole versus letrozole alone (2.5 mg OD on a continuous regimen) in post-menopausal women with ER+, HER2- advanced breast cancer. Study achieved its primary endpoint by demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for the combination of palbociclib and letrozole compared with letrozole alone. Detailed efficacy and safety data from PALOMA-1 will be submitted for presentation at the American Association for Cancer Research (AACR) Annual Meeting 2014, April 5-9th, San Diego. [6]
04/02/2014 10:24:11
Jan 13: NCT01740427 is a randomized, multicentre, double-blind PIII study of PD-0332991 + letrozole vs placebo + letrozole for the treatment of 450 postmenopausal women with ER (+), HER2 (-) breast cancer who have not received any prior systemic anti cancer treatment for advanced disease. PD-0332991 125mg is given once daily on day 1 to day 21 of every 28-day cycle. The primary outcome is PFS. The study starts Feb 13 and is due to complete Aug 15 [3].
15/01/2013 14:52:48
Results from part 1 of a PI/II study of letrozole with or without PD 0332991 for the first-line treatment of estrogen-receptor positive, HER2-negative advanced breast cancer presented at the 2012 IMPAKT Breast Cancer Conference and showed statistically significant improvement in median progression-free survival (PFS) in the PD 0332991 plus letrozole arm. The most commonly reported AEs were neutropenia, leucopenia, and fatigue [2]
15/01/2013 14:51:40
References
Available only to registered users
Category
BNF Category: Other antineoplastic drugs (08.01.05)
Pharmacology: Pyridopyrimidine-derived cyclin-dependent kinase (CDK) 4 & 6 inhibitor
Epidemiology: The incidence of BC in the UK is about 80 per 100,000 people. About 40% develop metastatic disease; 75% of these are HER2-negative.
Indication: Breast cancer
Additional Details: 1st line + letrozole, advanced or metastatic, ER+ HER-
Method(s) of Administration
Oral
Company Information
Name: Pfizer
US Name: Pfizer
Further Information
Anticipated Commissioning route (England) -
In timetable: -
PbR Awaiting Update
PBR Chemotherapy is locally negotiated.
Implications Available only to registered users
http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm432871.htm