J. Randolph Hecht, Zev A. Wainberg, and Dennis Slamon, David Geffen School of Medicine, University of California Los Angeles, Santa Monica; Michael F. Press, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA; Yung-Jue Bang, Seoul National University College of Medicine; Hyun C. Chung, Yonsei Cancer Center, Yonsei Cancer Research Institute, Yonsei University College of Medicine; Joon O. Park, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Shukui K. Qin, People's Liberation Army Cancer Center, Nanjing Bayi Hospital, Jiangsu; Jianming M. Xu, Affiliated Hospital of the Military Medical Science Academy, Beijing; Jin Li, Cancer Hospital of Shanghai Fudan University, Shanghai, People's Republic of China; Krzysztof Jeziorski, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; Yaroslav Shparyk, Lviv State Regional Oncology Medical and Diagnostic Center, Lviv, Ukraine; Paulo M. Hoff, Sociedade Beneficente de Senhoras-Hospital Sirio Libanĕs, Sao Paolo, Brazil; Alberto Sobrero, Istituto di Ricovero e Cura a Carattere Scientifico San Martino Istituto Scientifico Tumori, Genova, Italy; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Svetlana A. Protsenko, Petrov Research Institute of Oncology, St Petersburg, Russia; Marc Buyse, International Drug Development Institute, Leuven, Belgium; Karen Afenjar, Vincent Houé, and Agathe Garcia, Translational Research in Oncology, Paris, France; Tomomi Kaneko and Saba Khan-Wasti, GlaxoSmithKline, Brentford, United Kingdom; and Yingjie Huang and Sergio Santillana, GlaxoSmithKline, Philadelphia, PA.
J Clin Oncol. 2016 Feb 10;34(5):443-51. doi: 10.1200/JCO.2015.62.6598. Epub 2015 Nov 30.
To 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 with HER2-positive advanced gastroesophageal adenocarcinoma were randomly assigned at a one-to-one ratio to CapeOx plus lapatinib 1,250 mg or placebo daily. Primary end point was overall survival (OS) in patients with centrally confirmed HER2 amplification in the primary efficacy population.
A 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.
Addition 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.
评估在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中，加用拉帕替尼对比安慰剂联合卡培他滨和奥沙利铂（CapeOx）的疗效。
HER2 阳性的晚期胃食管腺癌患者以 1:1 的比例随机分配，接受 CapeOx 联合拉帕替尼 1250mg 或安慰剂每日治疗。主要终点是在主要疗效人群中经中心确认的 HER2 扩增患者的总生存期（OS）。
共随机分配了 545 例患者，其中 487 例患者纳入主要疗效人群。拉帕替尼组和安慰剂组的中位 OS 分别为 12.2 个月（95%CI，10.6 至 14.2）和 10.5 个月（95%CI，9.0 至 11.3），差异无统计学意义（风险比，0.91；95%CI，0.73 至 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 至 7.0）和 5.4 个月（95%CI，4.4 至 5.7），差异有统计学意义（风险比，0.82；95%CI，0.68 至 1.00；P=0.0381）。拉帕替尼组的缓解率显著高于安慰剂组：53%（95%CI，46.4 至 58.8）比 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 免疫组织化学状态与生存之间无相关性。拉帕替尼组的毒性反应增加，特别是腹泻。
在 HER2 扩增的胃食管腺癌患者中，加用拉帕替尼并未增加 CapeOx 的 OS。拉帕替尼的疗效因地区和年龄而异。未来的研究可以进一步研究这种相关性。
