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

J. Randolph Hecht, Yung Jue Bang, Shukui K. Qin, Hyun C. Chung, Jianming M. Xu, Joon O. Park, Krzysztof Jeziorski, Yaroslav Shparyk, Paulo M. Hoff, Alberto Sobrero, Pamela Salman, Jin Li, Svetlana A. Protsenko, Zev A. Wainberg, Marc Buyse, Karen Afenjar, Vincent Houè, Agathe Garcia, Tomomi Kaneko, Yingjie HuangSaba Khan-Wasti, Sergio Santillana, Michael F. Press, Dennis Slamon

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Abstract

Purpose: 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 and Methods: Patients 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 patientswith centrally confirmed HER2 amplification in the primary efficacy population. Results: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)443-451
Number of pages9
JournalJournal of Clinical Oncology
Volume34
Issue number5
DOIs
Publication statusPublished - 2016 Feb 10

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Hecht, J. R., Bang, Y. J., Qin, S. K., Chung, H. C., Xu, J. M., Park, J. O., Jeziorski, K., Shparyk, Y., Hoff, P. M., Sobrero, A., Salman, P., Li, J., Protsenko, S. A., Wainberg, Z. A., Buyse, M., Afenjar, K., Houè, V., Garcia, A., Kaneko, T., ... Slamon, D. (2016). 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. Journal of Clinical Oncology, 34(5), 443-451. https://doi.org/10.1200/JCO.2015.62.6598