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2015年ASCO年会将于5月29日--6月2日在美国芝加哥召开，5月31日上午的非小细胞肺癌（NSCLC）口头报告专场，将公布LUX-Lung8（LL8）研究的总生存期结果，该研究对比了阿法替尼（A）和厄洛替尼（E）用于晚期肺鳞状细胞癌（SCC）患者二线治疗的疗效，患者之前接受铂类为基础的化疗。下面和大家提前分享这项研究的摘要。

背景：晚期肺鳞癌患者在铂类为基础的化疗之后针对疾病进展的治疗方案还比较有限。SCC的病理学发现EGFR、ErbB受体过表达和下游通路失调参与其中。LL8（肺鳞癌患者二线A vs E；A为不可逆的ErbB家族抑制剂，E为可逆的EGFR酪氨酸激酶抑制剂）的初步分析显示阿法替尼可带来更好的无进展生存期（PFS）。本研究报告了OS和更新的PFS数据。

方法：IIIB/IV期患者1:1随机分配接受阿法替尼（40mg/d）或厄洛替尼（150mg/d）治疗直到疾病进展。主要终点。PFS；关键的次要终点：OS。其他终点：客观缓解率（ORR），疾病控制率（DCR），患者报告的结局，安全性。

结果：相比于接受厄洛替尼（n=397）治疗，阿法替尼组（n=398）的OS明显更好，可降低19%的死亡风险（中位OS：7.9 vs 6.8个月；HR，0.81；95%CI，0.69-095；p=0.008）。在6个月（63.6 vs 54.6%；p=0.010）、12个月（36.4 vs 28.2%；p=0.016）和18个月（22.0 vs 14.4%；p=0.013）可以看到OS的明显差异。阿法替尼的PFS（2.6 vs 1.9个月；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）也明显更优。

阿法替尼组有更多的患者出现整体健康状况/质量（35.7 vs 28.3%；p=0.041）、咳嗽（43.4 vs 35.2%；p=0.029）和呼吸困难（51.3 vs 44.1%；p=0.061）等症状的改善。两组的不良反应发生情况具有可比性（三级及以上的不良反应，A vs E：57.1% vs 57.5%）。阿法替尼组的药物相关3/4级腹泻（9.9/0.5 vs 2.3/0.3%）、3级口腔炎（4.1 vs 0%）的发生率更高。厄洛替尼组的3级皮疹/痤疮的发生率更高（5.9 vs 10.4%）。

结论：对于肺鳞癌患者的二线治疗，阿法替尼相比厄洛替尼能明显改善OS，PFS和DCR也明显更好。此外，LL8研究中可以看到阿法替尼的不良反应可控，还可带来生活质量的获益以及症状控制，对于该类患者，阿法替尼应该更优于厄洛替尼。临床试验信息：NCT01523587

会议专题》》》2015年ASCO年会专题报道

阅读摘要原文

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) analysis from the global phase III trial LUX-Lung 8 (LL8).（Abstract No:8002）

Author(s): Jean-Charles Soria, Enriqueta Felip, Manuel Cobo, et al

Session 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 analysis 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 analysis 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 information: NCT01523587

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