2015年ASCO年會(huì)將于5月29日--6月2日在美國(guó)芝加哥召開(kāi)，5月31日上午的非小細(xì)胞肺癌（NSCLC）口頭報(bào)告專(zhuān)場(chǎng)，將公布LUX-Lung8（LL8）研究的總生存期結(jié)果，該研究對(duì)比了阿法替尼（A）和厄洛替尼（E）用于晚期肺鱗狀細(xì)胞癌（SCC）患者二線治療的療效，患者之前接受鉑類(lèi)為基礎(chǔ)的化療。下面和大家提前分享這項(xiàng)研究的摘要。

    背景：晚期肺鱗癌患者在鉑類(lèi)為基礎(chǔ)的化療之后針對(duì)疾病進(jìn)展的治療方案還比較有限。SCC的病理學(xué)發(fā)現(xiàn)EGFR、ErbB受體過(guò)表達(dá)和下游通路失調(diào)參與其中。LL8（肺鱗癌患者二線A vs E;A為不可逆的ErbB家族抑制劑，E為可逆的EGFR酪氨酸激酶抑制劑）的初步分析顯示阿法替尼可帶來(lái)更好的無(wú)進(jìn)展生存期（PFS）。本研究報(bào)告了OS和更新的PFS數(shù)據(jù)。

    方法：IIIB/IV期患者1:1隨機(jī)分配接受阿法替尼（40mg/d）或厄洛替尼（150mg/d）治療直到疾病進(jìn)展。主要終點(diǎn)。PFS;關(guān)鍵的次要終點(diǎn)：OS.其他終點(diǎn)：客觀緩解率（ORR），疾病控制率（DCR），患者報(bào)告的結(jié)局，安全性。

    結(jié)果：相比于接受厄洛替尼（n=397）治療，阿法替尼組（n=398）的OS明顯更好，可降低19%的死亡風(fēng)險(xiǎn)（中位OS:7.9 vs 6.8個(gè)月；HR,0.81;95%CI,0.69-095;p=0.008）。在6個(gè)月（63.6 vs 54.6%;p=0.010）、12個(gè)月（36.4 vs 28.2%;p=0.016）和18個(gè)月（22.0 vs 14.4%;p=0.013）可以看到OS的明顯差異。阿法替尼的PFS（2.6 vs 1.9個(gè)月；HR,0.81;95%CI,0.69-0.96;p=0.010）、ORR（5.5 vs 2.8%;p=0.055）和DCR（50.5 vs 39.5%;p=0.002）也明顯更優(yōu)。

    阿法替尼組有更多的患者出現(xiàn)整體健康狀況/質(zhì)量（35.7 vs 28.3%;p=0.041）、咳嗽（43.4 vs 35.2%;p=0.029）和呼吸困難（51.3 vs 44.1%;p=0.061）等癥狀的改善。兩組的不良反應(yīng)發(fā)生情況具有可比性（三級(jí)及以上的不良反應(yīng)，A vs E:57.1% vs 57.5%）。阿法替尼組的藥物相關(guān)3/4級(jí)腹瀉（9.9/0.5 vs 2.3/0.3%）、3級(jí)口腔炎（4.1 vs 0%）的發(fā)生率更高。厄洛替尼組的3級(jí)皮疹/痤瘡的發(fā)生率更高（5.9 vs 10.4%）。

    結(jié)論：對(duì)于肺鱗癌患者的二線治療，阿法替尼相比厄洛替尼能明顯改善OS,PFS和DCR也明顯更好。此外，LL8研究中可以看到阿法替尼的不良反應(yīng)可控，還可帶來(lái)生活質(zhì)量的獲益以及癥狀控制，對(duì)于該類(lèi)患者，阿法替尼應(yīng)該更優(yōu)于厄洛替尼。臨床試驗(yàn)信息：NCT01523587

    閱讀摘要原文

    Afatinib （A） vs erlotinib （E） as second-line therapy of patients （pts） with advanced squamous cell carcinoma （SCC） of the lung following platinum-based chemotherapy: Overall survival （OS） **ysis from the global phase III trial LUX-Lung 8 （LL8）。（Abstract No:8002）Author（s）： Jean-Charles Soria, Enriqueta Felip, Manuel Cobo, et alSession Type: Oral Abstract Session

    Background: Treatment options for pts with advanced SCC of the lung progressing after platinum-based chemotherapy are limited. Overexpression of EGFR, ErbB receptors and the dysregulation of their downstream pathways are implicated in SCC pathobiology. Primary **ysis of LL8 （2nd line A, an irreversible ErbB family blocker vs E, a reversible EGFR tyrosine kinase inhibitor [TKI; only TKI approved in this setting], in pts with SCC of the lung） showed significantly better progression-free survival （PFS） with A. OS and updated PFS are reported here.

    Methods: Pts with stage IIIB/IV disease were randomized 1:1 to receive A （40 mg/day） or E （150 mg/day） until disease progression. Primary endpoint: PFS; key secondary endpoint: OS. Other endpoints: objective response （ORR）， disease control （DCR）， patient reported outcomes and safety. 632 events and a sample size of 800 pts was needed to detect a HR of 0.8 with 80% power for OS.

    Results: OS was significantly better with A （n = 398） vs E （n = 397）， with a 19% reduced risk of death （median 7.9 vs 6.8 mos; HR [95% CI] 0.81 [0.69–0.95]; p = 0.008）。 Significant differences in OS were seen at 6 （63.6 vs 54.6%; p = 0.010）， 12 （36.4 vs 28.2%; p = 0.016） and 18 （22.0 vs 14.4%; p = 0.013） mos. PFS （median 2.6 vs 1.9 mos; HR [95% CI] 0.81 [0.69–0.96]; p = 0.010）， ORR （5.5 vs 2.8%; p = 0.055） and DCR （50.5 vs 39.5%; p = 0.002） were all better for A vs E. More pts had improved global health status/quality of life （35.7 vs 28.3%; p = 0.041）， cough （43.4 vs 35.2%; p = 0.029） and dyspnea （51.3 vs 44.1%; p = 0.061） with A vs E. Adverse event （AE） profiles were comparable （G ≥ 3 AEs: 57.1 and 57.5% for A vs E） with a higher incidence of drug-related G3/4 diarrhea （9.9/0.5 vs 2.3/0.3%）， G3 stomatitis （4.1 vs 0%） with A and a higher incidence of G3 rash/acne with E （5.9 vs 10.4%）。 Preliminary data from FoundationOne **ysis of tumor blocks will be shown.

    Conclusions: A significantly improved OS vs E in pts with SCC of the lung in a 2nd line setting. PFS and DCR were also significantly better. With a manageable AE profile, added QoL benefit, and symptom control seen in LL8, A should be preferred over E for these pts. Clinical trial ***rmation: NCT01523587