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.

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 1,250 mg or placebo daily. Primary end point was overall survival (OS) in patients with 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.

• Authors: 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 Houé, Agathe Garcia, Tomomi Kaneko, Yingjie Huang, Saba Khan-Wasti, Sergio Santillana, Michael F Press, Dennis Slamon
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 34 Issue 5 Pg. 443-51 (Feb 10 2016) ISSN: 1527-7755 [Electronic] United States
• PMID: 26628478 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by American Society of Clinical Oncology.

Chemical References

• Biomarkers, Tumor
• Organoplatinum Compounds
• Quinazolines
• Oxaliplatin
• Lapatinib
• Capecitabine
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adenocarcinoma (drug therapy, genetics, mortality, secondary)
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (genetics)
• Capecitabine (administration & dosage)
• Double-Blind Method
• Esophageal Neoplasms (drug therapy, genetics, mortality, pathology)
• Esophagogastric Junction (drug effects, pathology)
• Female
• Follow-Up Studies
• Gene Amplification
• Humans
• Lapatinib
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Staging
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Polymerase Chain Reaction
• Prognosis
• Quinazolines (administration & dosage)
• Receptor, ErbB-2 (genetics)
• Stomach Neoplasms (drug therapy, genetics, mortality, pathology)
• Survival Rate
• Young Adult