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J Clin Oncol. 2016 Feb 10;34(5):443-51. doi: 10.1200/JCO.2015.62.6598. Epub 2015 Nov 30.

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.

Author information

1
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. jrhecht@mednet.ucla.edu.
2
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.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00680901.

PMID:
26628478
DOI:
10.1200/JCO.2015.62.6598
[Indexed for MEDLINE]

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