2014年11月28日，欧洲药品管理局（EMA）人用医药产品委员会（CHMP）已建议批准抗癌药物Ofev（nintedanib）用于特发性肺纤维化（IPF）的治疗。近日，欧盟委员会（EC）已批准nintedanib联合多西紫杉醇（docetaxel）用于一线化疗后腺癌肿瘤学为局部晚期或转移性复发性非小细胞肺癌（NSCLC）患者的治疗，品牌名为Vargatef。
nintedanib联合化疗，是首个在起始化疗失败的广泛腺癌群体中延长患者生存期超过1年的肺癌药物。nintedanib是勃林格殷格翰肿瘤学管线中的第2种抗癌药，首个肿瘤学药物Giotrif（afatinib）于2013年获批在美欧2大主要市场上市，用于携带激活性EGFR突变的局部晚期或转移性非小细胞肺癌（NSCLC）初治成人患者的治疗。
Vargatef（nintedanib）的获批，是基于一项国际性、双盲III期LUME-Lung 1研究的数据，这是在广泛的二线腺癌患者群体所开展的、附加疗法表现出相对于活性对照组具有生存利益的首个试验。该项试验在NSCLC患者中开展，与安慰剂+多西紫杉醇组相比，nintedanib+多西紫杉醇治疗组疾病无进展生存期（PFS）表现出统计学意义的显著延长（3.4个月 vs 2.7个月），肿瘤再度生长风险降低21%，总生存期（OS）显著延长（12.6个月 vs 10.3个月），平均延长20%。此外，数据还表明，腺癌患者越早发生一线化疗失败，nintedanib所带来的临床益处越大，在初始一线治疗后9个月内（T＜9个月）疾病恶化的患者，平均总生存期取得了3个月的临床益处（10.9个月 vs 7.9个月）。
Nintedanib是一种口服三联血管激酶抑制剂，可同时阻断3种生长因子受体：血管内皮生长因子受体（VEGFR 1-3）、血小板源性生长因子受体（PDGFR α和β）、成纤维细胞生长因子受体（FGFR 1-3）。所有这3种受体在血管生成和肿瘤生长过程中均发挥着重要作用。这些受体的阻断，可能导致血管生成的抑制，而血管生成在肿瘤生长中起着关键作用。
在欧盟，CHMP近日已建议批准nintedanib用于特发性肺纤维化（IPF）的治疗。在美国，FDA已批准Ofev（nintedanib）用于特发性肺纤维化（IPF）适应症，同时获批的还有罗氏和InterMune的另一款特发性肺纤维化（IPF）药物Esbriet（比非尼酮）。
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New Drugs Online Report for nintedanib
Information
Generic Name: nintedanib
Trade Name: Vargatef
Synonym: BIBF 1120, nintedanib
Entry Type: New molecular entity
Development and Regulatory status
UK: Launched
EU: Launched
US: Phase III Clinical Trials
UK launch Plans: Available only to registered users
Actual UK launch date: January 2015
Comments
Jan 15: launched 27/1/15. The recommended dose of nintedanib is 200mg twice daily on days 2 to 21 of a standard 21 day docetaxel treatment cycle. NHS cost for 120x100mg caps is £2,151.10 [15]
27/01/2015 12:06:39
Nov 14: European Commission approves use of nintedanib in NSCLC [13].
28/11/2014 09:59:49
Sep 14: EU positive opinion for use in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent NSCLC) of adenocarcinoma tumour histology after first-line chemotherapy [12].
29/09/2014 12:09:59
Oct 13: Filed in EU for treatment of patients with advanced NSCLC of adenocarcinoma histology after first line chemotherapy, in combination with docetaxel [10].
15/10/2013 14:11:14
May 13: LUME Lung-1 complete (currently no results available) and LUME Lung-2 due to end Dec 13 [7].
23/05/2013 09:28:07
Apr 12: Results from LUME Lung-1 and 2 not expected until H1 2013 [6].
20/04/2012 16:46:22
Launch anticipated early 2013 (5)
09/05/2011 15:49:43
EU submission expected Q2 2011 (4)
23/03/2010 12:27:01
EU submission expcted Q4 2010 (3)
12/08/2009 11:23:58
Trial or other data
Dec 14: In DRAFT guidance, NICE does not recommend the use of nintedanib in combination with docetaxel for treating locally advanced, metastatic or locally recurrent non-small-cell lung cancer of adenocarcinoma histology that has progressed after first-line chemotherapy. [14]
24/12/2014 10:07:08
Jan 14: LUME-Lung 1 trial published in The Lancet [11].
10/01/2014 12:02:43
Sep 13: Further analysis of the PIII LUME-Lung 1 trial presented at the European Cancer Congress shows that the earlier adenocarcinoma patients failed first-line chemotherapy, the bigger the benefit that nintedanib provided. Pts whose disease progressed within nine months of starting first-line treatment achieved a larger median OS benefit of 3 months (10.9 with nintedanib plus docetaxel vs 7.9 months with placebo plus docetaxel) [9].
30/09/2013 12:34:46
Jun 13: Top line results reported from the LUME-Lung 1 trial (n=1,314). Median PFS in the nintedanib /docetaxel arm was 3.4 months vs 2.7 months in the docetaxel-only group (HR 0.79; p=0.0019). Median OS , a secondary endpoint, was 10.1 vs 9.1 months, respectively (HR 0.94; p=0.272), but there was a 2.3 month advantage in patients with adenocarcinoma histology (median OS 12.6 vs 10.3 months , HR 0.83, p=0.0359) [8].
04/06/2013 09:14:04
Phase III clinical trials: LUME-Lung 1 and LUME-Lung 2. BIBF 1120 will be assessed as a second-line therapy in combination with standard chemotherapy agents. Approximately 2,600 patients are expected to be recruited into the phase III programme. (2)
12/05/2009 14:57:20
BIBF 1120 inhibits three kinases involved in the development of tumour blood vasculature; vascular endothelial growth factor receptor 2 (VEGFR-2), fibroblast growth factor receptor (FGFR) and platelet-derived growth factor receptor (PDGFR).(2)
12/05/2009 14:54:49
Evidence Based eva luations
EPAR http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002569/WC500179972.pdf
NICE TA http://www.nice.org.uk/guidance/indevelopment/gid-tag449/consultation
NICE scope http://www.nice.org.uk/Guidance/InDevelopment/GID-TAG449/Documents
NHSC http://www.nhsc-healthhorizons.org.uk/files/downloads/1103/1609.89fd4bf4e5e78d21983db3eda26124a0.pdf
References
Available only to registered users
Category
BNF Category: Other antineoplastic drugs (08.01.05)
Pharmacology: Inhibitor of VEGFR-2, FGFR and PDGFR
Epidemiology: The incidence rate of lung cancer in 2006 was 72.2 per 100,000 in men and 50.8 per 100,000 in women. Lung cancer belongs to the three most common cancers in men (14.8 % of all cancers) and women (10.9% of all cancers).
Indication: Non-small cell lung cancer (NSCLC)
Additional Details: 2nd line treatment in combi with pemetrexed or docetaxel
Method(s) of Administration
Oral
Company Information
Name: Boehringer Ingelheim
US Name: Boehringer Ingelheim
Further Information
Anticipated commissioning route (England) NHSE
High cost drug list? Awaiting Update
Tariff Chemotherapy tariff
In NICE timetable: Yes
When: Apr / 2015
Note: www.nice.org.uk/Guidance/InDevelopment/GID-TAG449
Implications Available only to registered users |
