Swedish Cancer Institute, Seattle, WA.
Southwestern Oncology Group Statistical Center, Seattle, WA.
Clin Lung Cancer. 2018 Jan;19(1):84-92. doi: 10.1016/j.cllc.2017.06.016. Epub 2017 Jul 6.
Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636).
Eligible patients with BAC or adenocarcinoma with BAC features (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636) received erlotinib 150 mg/day with bevacizumab 15 mg/kg until progression or prohibitive toxicity. Never smokers with BAC were preferentially enrolled to SWOG S0636. The primary endpoint for both trials was overall survival.
A total of 84 patients were enrolled in the SWOG S0635 trial and 85 in the SWOG S0636 trial. The objective response rate was 22% (3% complete response) in the SWOG S0635 trial and 50% (38% confirmed; 3% complete response) in the SWOG S0636 trial. The median progression-free survival was 5 and 7.4 months in the S0635 and S0636 trials, respectively. The median overall survival was 21 and 29.8 months, respectively. Toxicity consisted mainly of rash and diarrhea in both trials.
Although the field has moved toward molecular, rather than clinical, selection of patients as optimal candidates for EGFR TKI therapy, these results support the hypothesis that a subset of patients in whom erlotinib is particularly active could receive an incremental benefit from the addition of bevacizumab.
在表皮生长因子受体（EGFR）基因突变检测被认为与 EGFR 酪氨酸激酶抑制剂（TKI）的活性高度相关之前，临床上已经确定了细支气管肺泡癌（BAC）和不吸烟患者人群可能从 EGFR TKI 中获益。基于临床前和临床数据表明，EGFR TKI 联合抗血管生成药物贝伐珠单抗可能具有潜在的更好疗效，西南肿瘤协作组（SWOG）启动了两项配对的 II 期临床试验，以评估厄洛替尼/贝伐珠单抗联合治疗晚期 BAC（SWOG S0635）或不吸烟的晚期肺腺癌（SWOG S0636）患者的疗效。
符合条件的 BAC 或具有 BAC 特征的腺癌（SWOG S0635）或不吸烟的晚期肺腺癌（SWOG S0636）患者接受厄洛替尼 150mg/天联合贝伐珠单抗 15mg/kg，直至疾病进展或出现无法耐受的毒性。不吸烟的 BAC 患者优先入组 SWOG S0636。两项试验的主要终点均为总生存期。
SWOG S0635 试验共入组 84 例患者，SWOG S0636 试验共入组 85 例患者。SWOG S0635 试验的客观缓解率为 22%（3%完全缓解），SWOG S0636 试验的客观缓解率为 50%（38%确认；3%完全缓解）。SWOG S0635 试验和 S0636 试验的中位无进展生存期分别为 5 个月和 7.4 个月。中位总生存期分别为 21 个月和 29.8 个月。两项试验的毒性主要为皮疹和腹泻。
尽管目前已经转向基于分子而非临床的患者选择，作为 EGFR TKI 治疗的最佳候选者，但这些结果支持了这样一种假设，即厄洛替尼特别活跃的患者亚组可能会从添加贝伐珠单抗中获得额外的获益。
