Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC-A Randomized Phase III Trial
Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC-A Randomized Phase III Trial
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DOI：
10.1200/jco.2015.62.6598
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发表时间：
2016-02-10
影响因子：
45.3
通讯作者：
Slamon, Dennis
中科院分区：
文献类型：
--
作者：
Hecht, J. Randolph;Bang, Yung-Jue;Slamon, Dennis
目的评价拉帕替尼联合卡培他滨和奥沙利铂（CapeOx）治疗未经治疗的人表皮生长因子受体2 （HER2）扩增的晚期胃食管腺癌患者的疗效。患者和方法：her2阳性晚期胃食管腺癌患者以1:1的比例随机分配至CapeOx +拉帕替尼1,250mg或安慰剂每日。主要终点是在主要有效人群中中心确认HER2扩增的患者的总生存期（OS）。结果共纳入545例患者，其中487例为主要有效人群。拉帕替尼组和安慰剂组的中位OS分别为12.2 （95% CI, 10.6 - 14.2）和10.5个月（95% CI, 9.0 - 11.3），两者无显著差异（风险比，0.91;95% CI, 0.73 - 1.12）。拉帕替尼组和安慰剂组的中位无进展生存期分别为6.0个月（95% CI, 5.6 - 7.0）和5.4个月（95% CI, 4.4 - 5.7）（风险比，0.82;95% CI, 0.68 - 1.00; P = 0.0381）。拉帕替尼组的反应率显著更高：53% (95% CI， 46.4至58.8)，而安慰剂组的反应率为39% (95% CI， 32.9至45.3)（P = 0.0031）。预先计划的探索性亚组分析显示，在亚洲和年轻患者中，拉帕替尼组的OS延长。HER2免疫组化状态与生存率无相关性。拉帕替尼组毒性增加，特别是腹泻。结论CapeOx加用拉帕替尼不会增加her2扩增型胃食管腺癌患者的OS。拉帕替尼的疗效在不同地区和年龄有明显差异。未来的研究可以检验这种相关性。(C) 2015年由美国临床肿瘤学会出版
PurposeTo evaluate the efficacy of adding lapatinib to capecitabine and oxaliplatin (CapeOx) in patients with previously untreated human epidermal growth factor receptor 2 (HER2) -amplified advanced gastroesophageal adenocarcinoma.Patients and MethodsPatients with HER2-positive advanced gastroesophageal adenocarcinoma were randomly assigned at a one-to-one ratio to CapeOx plus lapatinib 1,250mg or placebo daily. Primary end point was overall survival (OS) in patients with centrally confirmed HER2 amplification in the primary efficacy population.ResultsA total of 545 patients were randomly assigned, and 487 patients comprised the primary efficacy population. Median OS in the lapatinib and placebo arms was 12.2 (95% CI, 10.6 to 14.2) and 10.5 months (95% CI, 9.0 to 11.3), respectively, which was not significantly different (hazard ratio, 0.91; 95% CI, 0.73 to 1.12). Median progression-free survival in the lapatinib and placebo arms was 6.0 (95% CI, 5.6 to 7.0) and 5.4 months (95% CI, 4.4 to 5.7), respectively (hazard ratio, 0.82; 95% CI, 0.68 to 1.00; P = .0381). Response rate was significantly higher in the lapatinib arm: 53% (95% CI, 46.4 to 58.8) compared with 39% (95% CI, 32.9 to 45.3) in the placebo arm (P = .0031). Preplanned exploratory subgroup analyses showed OS in the lapatinib arm was prolonged in Asian and younger patients. No correlation was observed between HER2 immunohistochemistry status and survival. There were increased toxicities in the lapatinib arm, particularly diarrhea.ConclusionAddition of lapatinib to CapeOx did not increase OS in patients with HER2-amplified gastroesophageal adenocarcinoma. There were clear differences in the effect of lapatinib depending on region and age. Future studies could examine this correlation. (C) 2015 by American Society of Clinical Oncology