Discordance in HER2 status in gastro-esophageal adenocarcinomas

A systematic review and meta-analysis

Aafke Creemers, Emil ter Veer, L de Waal, P. Lodder, G.K.J. Hooijer, N.C.T. van Grieken, M.F. Bijlsma, S.L. Meijer, M.G.H. van Oijen, H.W.M. van Laarhoven

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Abstract

Trastuzumab combined with chemotherapy is standard of care for HER2 positive advanced gastro-esophageal cancers. The reported prevalence of HER2 discordance between primary tumors and corresponding metastases varies, hampering uniform patient selection for HER2 targeted therapy. This meta-analysis explores the influence of HER2 assessment methods on this discordance and investigates the prevalence of HER2 discordance in gastro-esophageal adenocarcinomas. PubMed, Embase and Cochrane databases were searched until January 2016. Differences in discordance rate between strict and broad(er) definitions of HER2 status were assessed using random-effect pair-wise meta-analysis. Random-effect single-arm meta-analyses were performed to assess HER2 discordance and the prevalence of positive and negative conversion. A significantly lower discordance rate in HER2 status between primary tumors and corresponding metastases was observed using a strict vs. broad definition of HER2 status (RR = 0.58, 95%CI 0.41–0.82), with a pooled discordance rate of 6.2% and 12.2%, respectively. Using the strict definition of HER2 assessment pooled overall discordance was 7% (95%CI 5–10%). The lowest discordance rates between primary tumors and corresponding metastasis are observed when using a strict method of HER2 positivity. Treatment outcomes of different studies will be better comparable if selection of eligible patients for HER2 targeted therapy is based on this strict definition.
Original languageEnglish
Article number3135
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 2017

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Esophageal Neoplasms
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Creemers, A., ter Veer, E., de Waal, L., Lodder, P., Hooijer, G. K. J., van Grieken, N. C. T., ... van Laarhoven, H. W. M. (2017). Discordance in HER2 status in gastro-esophageal adenocarcinomas: A systematic review and meta-analysis. Scientific Reports, 7, [3135]. https://doi.org/10.1038/s41598-017-03304-9
Creemers, Aafke ; ter Veer, Emil ; de Waal, L ; Lodder, P. ; Hooijer, G.K.J. ; van Grieken, N.C.T. ; Bijlsma, M.F. ; Meijer, S.L. ; van Oijen, M.G.H. ; van Laarhoven, H.W.M. / Discordance in HER2 status in gastro-esophageal adenocarcinomas : A systematic review and meta-analysis. In: Scientific Reports. 2017 ; Vol. 7.
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title = "Discordance in HER2 status in gastro-esophageal adenocarcinomas: A systematic review and meta-analysis",
abstract = "Trastuzumab combined with chemotherapy is standard of care for HER2 positive advanced gastro-esophageal cancers. The reported prevalence of HER2 discordance between primary tumors and corresponding metastases varies, hampering uniform patient selection for HER2 targeted therapy. This meta-analysis explores the influence of HER2 assessment methods on this discordance and investigates the prevalence of HER2 discordance in gastro-esophageal adenocarcinomas. PubMed, Embase and Cochrane databases were searched until January 2016. Differences in discordance rate between strict and broad(er) definitions of HER2 status were assessed using random-effect pair-wise meta-analysis. Random-effect single-arm meta-analyses were performed to assess HER2 discordance and the prevalence of positive and negative conversion. A significantly lower discordance rate in HER2 status between primary tumors and corresponding metastases was observed using a strict vs. broad definition of HER2 status (RR = 0.58, 95{\%}CI 0.41–0.82), with a pooled discordance rate of 6.2{\%} and 12.2{\%}, respectively. Using the strict definition of HER2 assessment pooled overall discordance was 7{\%} (95{\%}CI 5–10{\%}). The lowest discordance rates between primary tumors and corresponding metastasis are observed when using a strict method of HER2 positivity. Treatment outcomes of different studies will be better comparable if selection of eligible patients for HER2 targeted therapy is based on this strict definition.",
author = "Aafke Creemers and {ter Veer}, Emil and {de Waal}, L and P. Lodder and G.K.J. Hooijer and {van Grieken}, N.C.T. and M.F. Bijlsma and S.L. Meijer and {van Oijen}, M.G.H. and {van Laarhoven}, H.W.M.",
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language = "English",
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Creemers, A, ter Veer, E, de Waal, L, Lodder, P, Hooijer, GKJ, van Grieken, NCT, Bijlsma, MF, Meijer, SL, van Oijen, MGH & van Laarhoven, HWM 2017, 'Discordance in HER2 status in gastro-esophageal adenocarcinomas: A systematic review and meta-analysis', Scientific Reports, vol. 7, 3135. https://doi.org/10.1038/s41598-017-03304-9

Discordance in HER2 status in gastro-esophageal adenocarcinomas : A systematic review and meta-analysis. / Creemers, Aafke; ter Veer, Emil; de Waal, L; Lodder, P.; Hooijer, G.K.J.; van Grieken, N.C.T.; Bijlsma, M.F.; Meijer, S.L.; van Oijen, M.G.H.; van Laarhoven, H.W.M.

In: Scientific Reports, Vol. 7, 3135, 2017.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Discordance in HER2 status in gastro-esophageal adenocarcinomas

T2 - A systematic review and meta-analysis

AU - Creemers, Aafke

AU - ter Veer, Emil

AU - de Waal, L

AU - Lodder, P.

AU - Hooijer, G.K.J.

AU - van Grieken, N.C.T.

AU - Bijlsma, M.F.

AU - Meijer, S.L.

AU - van Oijen, M.G.H.

AU - van Laarhoven, H.W.M.

PY - 2017

Y1 - 2017

N2 - Trastuzumab combined with chemotherapy is standard of care for HER2 positive advanced gastro-esophageal cancers. The reported prevalence of HER2 discordance between primary tumors and corresponding metastases varies, hampering uniform patient selection for HER2 targeted therapy. This meta-analysis explores the influence of HER2 assessment methods on this discordance and investigates the prevalence of HER2 discordance in gastro-esophageal adenocarcinomas. PubMed, Embase and Cochrane databases were searched until January 2016. Differences in discordance rate between strict and broad(er) definitions of HER2 status were assessed using random-effect pair-wise meta-analysis. Random-effect single-arm meta-analyses were performed to assess HER2 discordance and the prevalence of positive and negative conversion. A significantly lower discordance rate in HER2 status between primary tumors and corresponding metastases was observed using a strict vs. broad definition of HER2 status (RR = 0.58, 95%CI 0.41–0.82), with a pooled discordance rate of 6.2% and 12.2%, respectively. Using the strict definition of HER2 assessment pooled overall discordance was 7% (95%CI 5–10%). The lowest discordance rates between primary tumors and corresponding metastasis are observed when using a strict method of HER2 positivity. Treatment outcomes of different studies will be better comparable if selection of eligible patients for HER2 targeted therapy is based on this strict definition.

AB - Trastuzumab combined with chemotherapy is standard of care for HER2 positive advanced gastro-esophageal cancers. The reported prevalence of HER2 discordance between primary tumors and corresponding metastases varies, hampering uniform patient selection for HER2 targeted therapy. This meta-analysis explores the influence of HER2 assessment methods on this discordance and investigates the prevalence of HER2 discordance in gastro-esophageal adenocarcinomas. PubMed, Embase and Cochrane databases were searched until January 2016. Differences in discordance rate between strict and broad(er) definitions of HER2 status were assessed using random-effect pair-wise meta-analysis. Random-effect single-arm meta-analyses were performed to assess HER2 discordance and the prevalence of positive and negative conversion. A significantly lower discordance rate in HER2 status between primary tumors and corresponding metastases was observed using a strict vs. broad definition of HER2 status (RR = 0.58, 95%CI 0.41–0.82), with a pooled discordance rate of 6.2% and 12.2%, respectively. Using the strict definition of HER2 assessment pooled overall discordance was 7% (95%CI 5–10%). The lowest discordance rates between primary tumors and corresponding metastasis are observed when using a strict method of HER2 positivity. Treatment outcomes of different studies will be better comparable if selection of eligible patients for HER2 targeted therapy is based on this strict definition.

U2 - 10.1038/s41598-017-03304-9

DO - 10.1038/s41598-017-03304-9

M3 - Article

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 3135

ER -