HER2 status in advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma for entry to the TRIO-013/LOGiC trial of lapatinib

Michael F. Press, Catherine E. Ellis, Robert C. Gagnon, Tobias J. Grob, Marc Buyse, Ivonne Villalobos, Zhiyong Liang, Shafei Wu, Yung Jue Bang, Shu Kui Qin, Hyuncheol Chung, Jianming Xu, Joon Oh Park, Krzysztof Jeziorski, Karen Afenjar, Yanling Ma, Monica C. Estrada, Douglas M. Robinson, Stefan J. Scherer, Guido Sauter & 2 others J. Randolph Hecht, Dennis J. Slamon

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Abstract

HER2/ERBB2 status is used to select patients for HER2-targeted therapy. HER2/ERBB2 amplification/overexpression of upper gastrointestinal (UGI) adenocarcinomas was determined locally or in two central laboratories to select patients for the TRIO-013/ LOGiC trial of chemotherapy with or without lapatinib. Patients selected locally had central laboratory confirmation of HER2 amplification for inclusion in the primary efficacy population. HER2 was assessed with PathVysion or IQ PharmDx FISH and HercepTest immunohistochemistry assays. Associations with outcomes were retrospectively evaluated. Overall, HER2 status was determined in UGI cancers from 4,674 patients in a central laboratory for eligibility (1,995 cases) and for confirmation of local HER2 results (333 cases). Of 1,995 adenocarcinomas screened centrally, 322 (16.1%) had HER2-amplified disease with 29 (1.5%) showing HER2 genomic heterogeneity. Men and older patients had higher rates of amplification. Of 545 patients accrued to the trial (gastric, 87.3%; GEJ, 8.3% and esophageal cancer, 4.4%), 487 patients (89%) were centrally confirmed as having HER2-amplified disease. Concordance between central and local HER2 testing was 83%. Concordance between PathVysion and IQ PharmDx FISH assays was 99% and FISH in the two central laboratories was 95%. Lapatinib-treated Asian participants and those less than 60 years had significant improvement in progression-free survival (PFS), particularly among those whose cancers had 5.01-10.0 and >10.0-fold amplification of HER2. In conclusion, HER2 is commonly amplified in UGI adenocarcinomas with amplification highly correlated to overexpression, and HER2 amplification levels correlated with PFS. While HER2 genomic heterogeneity occurs, its prevalence is low.

Original languageEnglish
Pages (from-to)228-238
Number of pages11
JournalMolecular Cancer Therapeutics
Volume16
Issue number1
DOIs
Publication statusPublished - 2017 Jan 1

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Stomach
Adenocarcinoma
Disease-Free Survival
Gastrointestinal Neoplasms
Esophageal Neoplasms
lapatinib
Immunohistochemistry
Drug Therapy
Population
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Press, Michael F. ; Ellis, Catherine E. ; Gagnon, Robert C. ; Grob, Tobias J. ; Buyse, Marc ; Villalobos, Ivonne ; Liang, Zhiyong ; Wu, Shafei ; Bang, Yung Jue ; Qin, Shu Kui ; Chung, Hyuncheol ; Xu, Jianming ; Park, Joon Oh ; Jeziorski, Krzysztof ; Afenjar, Karen ; Ma, Yanling ; Estrada, Monica C. ; Robinson, Douglas M. ; Scherer, Stefan J. ; Sauter, Guido ; Hecht, J. Randolph ; Slamon, Dennis J. / HER2 status in advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma for entry to the TRIO-013/LOGiC trial of lapatinib. In: Molecular Cancer Therapeutics. 2017 ; Vol. 16, No. 1. pp. 228-238.
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abstract = "HER2/ERBB2 status is used to select patients for HER2-targeted therapy. HER2/ERBB2 amplification/overexpression of upper gastrointestinal (UGI) adenocarcinomas was determined locally or in two central laboratories to select patients for the TRIO-013/ LOGiC trial of chemotherapy with or without lapatinib. Patients selected locally had central laboratory confirmation of HER2 amplification for inclusion in the primary efficacy population. HER2 was assessed with PathVysion or IQ PharmDx FISH and HercepTest immunohistochemistry assays. Associations with outcomes were retrospectively evaluated. Overall, HER2 status was determined in UGI cancers from 4,674 patients in a central laboratory for eligibility (1,995 cases) and for confirmation of local HER2 results (333 cases). Of 1,995 adenocarcinomas screened centrally, 322 (16.1{\%}) had HER2-amplified disease with 29 (1.5{\%}) showing HER2 genomic heterogeneity. Men and older patients had higher rates of amplification. Of 545 patients accrued to the trial (gastric, 87.3{\%}; GEJ, 8.3{\%} and esophageal cancer, 4.4{\%}), 487 patients (89{\%}) were centrally confirmed as having HER2-amplified disease. Concordance between central and local HER2 testing was 83{\%}. Concordance between PathVysion and IQ PharmDx FISH assays was 99{\%} and FISH in the two central laboratories was 95{\%}. Lapatinib-treated Asian participants and those less than 60 years had significant improvement in progression-free survival (PFS), particularly among those whose cancers had 5.01-10.0 and >10.0-fold amplification of HER2. In conclusion, HER2 is commonly amplified in UGI adenocarcinomas with amplification highly correlated to overexpression, and HER2 amplification levels correlated with PFS. While HER2 genomic heterogeneity occurs, its prevalence is low.",
author = "Press, {Michael F.} and Ellis, {Catherine E.} and Gagnon, {Robert C.} and Grob, {Tobias J.} and Marc Buyse and Ivonne Villalobos and Zhiyong Liang and Shafei Wu and Bang, {Yung Jue} and Qin, {Shu Kui} and Hyuncheol Chung and Jianming Xu and Park, {Joon Oh} and Krzysztof Jeziorski and Karen Afenjar and Yanling Ma and Estrada, {Monica C.} and Robinson, {Douglas M.} and Scherer, {Stefan J.} and Guido Sauter and Hecht, {J. Randolph} and Slamon, {Dennis J.}",
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Press, MF, Ellis, CE, Gagnon, RC, Grob, TJ, Buyse, M, Villalobos, I, Liang, Z, Wu, S, Bang, YJ, Qin, SK, Chung, H, Xu, J, Park, JO, Jeziorski, K, Afenjar, K, Ma, Y, Estrada, MC, Robinson, DM, Scherer, SJ, Sauter, G, Hecht, JR & Slamon, DJ 2017, 'HER2 status in advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma for entry to the TRIO-013/LOGiC trial of lapatinib', Molecular Cancer Therapeutics, vol. 16, no. 1, pp. 228-238. https://doi.org/10.1158/1535-7163.MCT-15-0887

HER2 status in advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma for entry to the TRIO-013/LOGiC trial of lapatinib. / Press, Michael F.; Ellis, Catherine E.; Gagnon, Robert C.; Grob, Tobias J.; Buyse, Marc; Villalobos, Ivonne; Liang, Zhiyong; Wu, Shafei; Bang, Yung Jue; Qin, Shu Kui; Chung, Hyuncheol; Xu, Jianming; Park, Joon Oh; Jeziorski, Krzysztof; Afenjar, Karen; Ma, Yanling; Estrada, Monica C.; Robinson, Douglas M.; Scherer, Stefan J.; Sauter, Guido; Hecht, J. Randolph; Slamon, Dennis J.

In: Molecular Cancer Therapeutics, Vol. 16, No. 1, 01.01.2017, p. 228-238.

Research output: Contribution to journalArticle

TY - JOUR

T1 - HER2 status in advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma for entry to the TRIO-013/LOGiC trial of lapatinib

AU - Press, Michael F.

AU - Ellis, Catherine E.

AU - Gagnon, Robert C.

AU - Grob, Tobias J.

AU - Buyse, Marc

AU - Villalobos, Ivonne

AU - Liang, Zhiyong

AU - Wu, Shafei

AU - Bang, Yung Jue

AU - Qin, Shu Kui

AU - Chung, Hyuncheol

AU - Xu, Jianming

AU - Park, Joon Oh

AU - Jeziorski, Krzysztof

AU - Afenjar, Karen

AU - Ma, Yanling

AU - Estrada, Monica C.

AU - Robinson, Douglas M.

AU - Scherer, Stefan J.

AU - Sauter, Guido

AU - Hecht, J. Randolph

AU - Slamon, Dennis J.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - HER2/ERBB2 status is used to select patients for HER2-targeted therapy. HER2/ERBB2 amplification/overexpression of upper gastrointestinal (UGI) adenocarcinomas was determined locally or in two central laboratories to select patients for the TRIO-013/ LOGiC trial of chemotherapy with or without lapatinib. Patients selected locally had central laboratory confirmation of HER2 amplification for inclusion in the primary efficacy population. HER2 was assessed with PathVysion or IQ PharmDx FISH and HercepTest immunohistochemistry assays. Associations with outcomes were retrospectively evaluated. Overall, HER2 status was determined in UGI cancers from 4,674 patients in a central laboratory for eligibility (1,995 cases) and for confirmation of local HER2 results (333 cases). Of 1,995 adenocarcinomas screened centrally, 322 (16.1%) had HER2-amplified disease with 29 (1.5%) showing HER2 genomic heterogeneity. Men and older patients had higher rates of amplification. Of 545 patients accrued to the trial (gastric, 87.3%; GEJ, 8.3% and esophageal cancer, 4.4%), 487 patients (89%) were centrally confirmed as having HER2-amplified disease. Concordance between central and local HER2 testing was 83%. Concordance between PathVysion and IQ PharmDx FISH assays was 99% and FISH in the two central laboratories was 95%. Lapatinib-treated Asian participants and those less than 60 years had significant improvement in progression-free survival (PFS), particularly among those whose cancers had 5.01-10.0 and >10.0-fold amplification of HER2. In conclusion, HER2 is commonly amplified in UGI adenocarcinomas with amplification highly correlated to overexpression, and HER2 amplification levels correlated with PFS. While HER2 genomic heterogeneity occurs, its prevalence is low.

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