勃林格殷格翰（Boehringer Ingelheim）宣布，抗癌藥物afatinib獲歐盟委員會(huì)（EC）批準(zhǔn)，作為一種單藥療法，用于攜帶激活性EGFR突變的局部晚期或轉(zhuǎn)移性非小細(xì)胞肺癌（NSCLC）初治成人患者的治療。在歐洲，afatinib將以品牌名Giotrif上市。
Giotrif的獲批，是基于關(guān)鍵性LUX-Lung 3臨床試驗(yàn)，這是在攜帶EGFR突變陽性肺癌患者中開展的迄今為止最大規(guī)模的的全球性III期試驗(yàn)，研究結(jié)果證實(shí)了afatinib在攜帶EGFR突變的IIIb或IV階段肺腺癌患者中相對(duì)于業(yè)界最佳化療藥物（培美曲塞和順鉑）的優(yōu)越性。
試驗(yàn)中，將afatinib作為一線治療藥物對(duì)患者進(jìn)行了治療，afatinib患者組疾病無進(jìn)展生存期（PFS）為11.1個(gè)月，而化療組（培美曲塞/順鉑）PFS為6.9個(gè)月。此外，針對(duì)攜帶2種最常見的EGFR突變（del19和L858R）的NSCLC，afatinib患者組PFS達(dá)13.6個(gè)月，而對(duì)照組僅為6.9個(gè)月。
Afatinib治療組疾病進(jìn)展延遲，患者大都經(jīng)歷了呼吸困難、氣短、咳嗽、胸痛等癥狀的改善，Afatinib也顯著延遲了這些癥狀的惡化。
Afatinib是勃林格殷格翰首個(gè)腫瘤學(xué)藥物，是首個(gè)不可逆ErbB家族阻斷劑，該藥積極的臨床證據(jù)，加上全新的作用模式，使其成為一種杰出的治療選擇，有望為肺癌患者提供其急需的臨床需求。
Afatinib于2013年7月15日獲得了FDA的批準(zhǔn)，以商品名Gilotrif上市，作為一種口服的、新的一線治療藥物，用于經(jīng)由FDA批準(zhǔn)的試劑盒證實(shí)腫瘤表皮生長因子受體（EGFR）19號(hào)外顯子缺失或21號(hào)外顯子突變（L858R）的轉(zhuǎn)移性非小細(xì)胞肺癌（NSCLC）患者的治療。
目前，勃林格殷格翰也已向亞洲及其他國家監(jiān)管當(dāng)局提交了afatinib的監(jiān)管審批，用于EGFR突變陽性的局部晚期和轉(zhuǎn)移性NSCLC的治療。（生物谷Bioon.com）
英文原文：GIOTRIF(afatinib) approved in Europe for patients with EGFR mutation positive lung cancer
INGELHEIM, Germany--(BUSINESSWIRE)-- For non U.S. Media Only
Boehringer Ingelheim announced today that the European Commission has granted marketing authorisation for afatinib monotherapy, for the treatment of Epidermal Growth Factor Receptor (EGFR) TKI-naïve adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutation(s). Afatinib will be marketed in Europe under the brand name GIOTRIF®.
“We are delighted with the decision by the European Commission. We hope this will be the first of many registrations for drugs from our in-house oncology research program,” commented Prof Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. “The approval of afatinib in Europe reinforces our commitment to bringing the right treatments to the right patients. This is a significant step towards meeting the substantial unmet need in lung cancer treatment.”
Lung cancer is one of the most common forms of cancer, accounting for 1.6 million new cases each year.2 It is the most deadly; more people die of lung cancer than of colon, breast and prostate cancers combined.3 In Europe alone, lung cancer is responsible for almost 270,000 deaths each year.4 Although incidence rates are higher in men than women it has been suggested that, by 2015, lung cancer will overtake breast cancer as the biggest cause of female cancer death in Europe.4
Because lung cancer is more than one disease, distinct subtypes can be characterised by receptors that are frequently altered or overexpressed in cancer cells. One such molecular marker is EGFR (a member of the ErbB Family of receptors). The prevalence of tumours harbouring EGFR mutations is between 10-15% in Caucasian and 40% in Asian NSCLC patients.5
In clinical trials, afatinib has been shown to offer patients with this type of lung cancer a significant delay in tumour progression, coupled with improvements in their lung cancer related symptoms (e.g. shortness of breath, cough and chest pain) and quality of life.1,6 Therefore, early mutation testing for EGFR status is a crucial step in the treatment-decision pathway, to give patients the opportunity to receive the appropriate personalised therapy from the start.
“Its unique mode of action allows afatinib to block EGFR and other members of the ErbB Family of receptors that play a key role in the growth and spread of cancers associated with a high mortality such as lung cancer,” said Dr. Sanjay Popat, Consultant Medical Oncologist, The Royal Marsden NHS Foundation Trust, London and clinical investigator in the LUX-Lung 3 trial. “Clinical data demonstrates afatinib’s efficacy in delaying tumour growth and improving lung cancer related symptoms, making it an important addition to our treatment options in Europe.”
Following recent approvals in the U.S., Taiwan and Mexico, European Union approval of afatinib is based on data from the pivotal LUX-Lung 3 trial and other Phase III and Phase II lung cancer studies. Data from Phase III LUX-Lung 3 trial have shown that patients taking afatinib as a first-line treatment lived for almost one year without their tumour growing again (median progression-free survival (PFS) of 11.1 months) versus just over half a year (PFS of 6.9 months) for those treated with pemetrexed/cisplatin. In addition, a subgroup analysis has shown that NSCLC patients with tumours harbouring the two most common EGFR mutations (Del19 or L858R) taking afatinib lived for well over a year without tumour progression (PFS of 13.6 months) versus just over half a year (PFS of 6.9 months) for those in the comparator arm.1
The most common grade 3 drug-related adverse events observed in the afatinib treatment arm were diarrhoea (14%), rash (16%), and inflammation of the nail bed (paronychia) (11%). The most common drug-related grade 3 adverse events observed in the chemotherapy arm (pemetrexed/cisplatin) were neutropenia (15%), fatigue (13%), and leucopenia (8%). There was a low discontinuation rate associated with treatment-related adverse events in the trial (8% discontinuation rate for afatinib; 12% for chemotherapy). 1% of patients in the afatinib arm discontinued due to drug-related diarrhoea.1
* In the EU, Taiwan and Mexico, afatinib is approved under the brand name GIOTRIF®, and in the U.S. under the brand name GILOTRIFTM for use in patients with distinct types of NSCLC. Afatinib is under regulatory review by health authorities in Asia and other countries.
