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

Research output: Contribution to journalArticle

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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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oxaliplatin
Stomach
Adenocarcinoma
Placebos
Survival
human ERBB2 protein
Capecitabine
lapatinib

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Hecht, J. Randolph ; Bang, Yung Jue ; Qin, Shukui K. ; Chung, Hyun C. ; Xu, Jianming M. ; Park, Joon O. ; Jeziorski, Krzysztof ; Shparyk, Yaroslav ; Hoff, Paulo M. ; Sobrero, Alberto ; Salman, Pamela ; Li, Jin ; Protsenko, Svetlana A. ; Wainberg, Zev A. ; Buyse, Marc ; Afenjar, Karen ; Houè, Vincent ; Garcia, Agathe ; Kaneko, Tomomi ; Huang, Yingjie ; Khan-Wasti, Saba ; Santillana, Sergio ; Press, Michael F. ; Slamon, Dennis. / 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. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 5. pp. 443-451.
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title = "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 1,250mg 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.",
author = "Hecht, {J. Randolph} and Bang, {Yung Jue} and Qin, {Shukui K.} and Chung, {Hyun C.} and Xu, {Jianming M.} and Park, {Joon O.} and Krzysztof Jeziorski and Yaroslav Shparyk and Hoff, {Paulo M.} and Alberto Sobrero and Pamela Salman and Jin Li and Protsenko, {Svetlana A.} and Wainberg, {Zev A.} and Marc Buyse and Karen Afenjar and Vincent Hou{\`e} and Agathe Garcia and Tomomi Kaneko and Yingjie Huang and Saba Khan-Wasti and Sergio Santillana and Press, {Michael F.} and Dennis Slamon",
year = "2016",
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Hecht, JR, Bang, YJ, Qin, SK, Chung, HC, Xu, JM, Park, JO, Jeziorski, K, Shparyk, Y, Hoff, PM, Sobrero, A, Salman, P, Li, J, Protsenko, SA, Wainberg, ZA, Buyse, M, Afenjar, K, Houè, V, Garcia, A, Kaneko, T, Huang, Y, Khan-Wasti, S, Santillana, S, Press, MF & 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, vol. 34, no. 5, pp. 443-451. https://doi.org/10.1200/JCO.2015.62.6598

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

In: Journal of Clinical Oncology, Vol. 34, No. 5, 10.02.2016, p. 443-451.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma

T2 - TRIO-013/LOGiC - A randomized phase III trial

AU - Hecht, J. Randolph

AU - Bang, Yung Jue

AU - Qin, Shukui K.

AU - Chung, Hyun C.

AU - Xu, Jianming M.

AU - Park, Joon O.

AU - Jeziorski, Krzysztof

AU - Shparyk, Yaroslav

AU - Hoff, Paulo M.

AU - Sobrero, Alberto

AU - Salman, Pamela

AU - Li, Jin

AU - Protsenko, Svetlana A.

AU - Wainberg, Zev A.

AU - Buyse, Marc

AU - Afenjar, Karen

AU - Houè, Vincent

AU - Garcia, Agathe

AU - Kaneko, Tomomi

AU - Huang, Yingjie

AU - Khan-Wasti, Saba

AU - Santillana, Sergio

AU - Press, Michael F.

AU - Slamon, Dennis

PY - 2016/2/10

Y1 - 2016/2/10

N2 - 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.

AB - 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.

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