ASCO 2012年会上公布了国际LUX-Lung3研究关于阿法替尼的结果，与培美曲塞联合顺铂的标准治疗方案相比，阿法替尼使具有1或2个常见EGFR突变的晚期肺腺癌患者的无进展生存翻倍，常见的EGFR突变包括外显子19缺失或外显子21 L858R突变，这两个突变占据所有EGFR突变的90%。

    中位随访8个月，研究者发现阿法替尼相比标准治疗可以延迟疾病进展超过4个月（11.1 vs 6.9个月；HR,0.58;95%CI,0.43-0.78;p=0.0004）。在具有外显子19缺失或外显子21 L858R突变的308名患者中，使用阿法替尼后的无进展生存延长更为明显（13.6 vs 6.9个月；HR,0.47;95%CI,0.34-0.65;p<0.0001）。

    阿法替尼是一种口服药物，是EGFR（ErbB1）和HER2（ErbB2）和ErbB4的不可逆抑制剂。LUX-Lung3是大的针对EGFR突变肺癌的前瞻性临床试验，第一次比较阿法替尼 vs 培美曲塞联合顺铂的疗效和安全。LUX-Lung1是2b/3期试验，其结果在2010年的ASCO年会上进行了公布，这项研究中，阿法替尼相比对照组延长了PFS（3.3 vs 1.1个月），此外，在8周的时候，阿法替尼组的肿瘤缩小比例显著高于安慰剂组（疾病控制率，58% vs 19%;P<0.0001）。

    阿法替尼在其他癌症中的应用也会在ASCO会议上公布，包括头颈部鳞癌（abstract TPS5598），HER2过表达的转移性乳腺癌（abstract TPS649），肺癌（abstracts 7557 and 7558）

    题目：LUX-Lung 3: A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations.（Abstract LBA7500）

    作者： James Chih-Hsin Yang, Martin H. Schuler, Nobuyuki Yamamoto,  et al.

    英文摘要

    Background: Afatinib （A） is a selective, orally bioavailable, irreversible ErbB family blocker of EGFR （ErbB1）， HER2 （ErbB2）， and ErbB4. This global study investigated the efficacy and safety of A compared with pemetrexed/cisplatin （PC） in pts with EGFR mutation positive advanced lung adenocarcinoma.

    Methods: Following central testing for EGFR mutations （companion diagnostic TheraScreen EGFR RGQ PCR kit）， 345 pts （stage IIIB/IV, PS 0–1, chemo-naive） were randomized 2:1 （A: 230; PC: 115） to daily A 40 mg or iv PC （500 mg/m2 + 75 mg/m2 q21 days up to 6 cycles）。 Primary endpoint was progression-free survival （PFS） by central independent review.

    Results: Baseline characteristics were balanced in both arms: median age, 61 y; female, 65%; Asian, 72%; never-smoker, 68%; Del19, 49%; L858R, 40%; other mutations, 11%. Treatment with A led to a significantly prolonged PFS vs PC （median 11.1 vs 6.9 mos; HR 0.58 [0.43–0.78]; p=0.0004）。 In 308 pts with common mutations （Del19/L858R）， median PFS was 13.6 vs 6.9 mos, respectively （HR=0.47 [0.34–0.65]; p<0.0001）。 Objective response rate was significantly higher with A （56% vs 23%; p<0.0001）。 Significant delay in time to deterioration of cancer-related symptoms of cough （HR=0.60, p=0.0072） and dyspnea （HR=0.68, p=0.0145） was seen with A vs PC. Most common drug-related adverse events （AEs） were diarrhea （95%）， rash （62%） and paronychia （57%） with A, and nausea （66%）， decreased appetite （53%） and vomiting （42%） with PC. Drug-related AEs led to discontinuation in 8% （A; 1% due to diarrhea） and 12% of pts （PC）。

    Conclusions: LUX-Lung 3 is the largest prospective trial in EGFR mutation positive lung cancer and the first study using pemetrexed/cisplatin as a comparator. Treatment with afatinib significantly prolonged PFS compared to PC, with significant improvements in secondary endpoints. AEs with afatinib were manageable, with a low discontinuation rate. With 4.2 mos PFS improvement in the overall population and 6.7 mos in pts with common mutations, afatinib is a clinically relevant first-line treatment option.