The Impact of Tumor Mutation Burden on the Effect of Frontline Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric Cancers

BackgroundTrastuzumab is a HER2-trargeted humanized monoclonal antibody that has been studied as a first-line treatment for patients with HER2-positive advanced gastric cancer (AGC). The effect of anti-HER2 therapy according to tumor mutational burden (TMB) in HER2-positive AGC remains unclear.Metho...

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Autores principales:	Hye Ryeon Kim, Soomin Ahn, Hyunji Jo, Hongsik Kim, Joohyun Hong, Jeeyun Lee, Ho-Yeong Lim, Won Ki Kang, Seung Tae Kim
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	trastuzumab advanced gastric cancer HER2 tumor mutational burden biomarker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/3aabafd8b49749279f87e8b796907259
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spelling	oai:doaj.org-article:3aabafd8b49749279f87e8b7969072592021-12-02T05:38:42ZThe Impact of Tumor Mutation Burden on the Effect of Frontline Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric Cancers2234-943X10.3389/fonc.2021.792340https://doaj.org/article/3aabafd8b49749279f87e8b7969072592021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.792340/fullhttps://doaj.org/toc/2234-943XBackgroundTrastuzumab is a HER2-trargeted humanized monoclonal antibody that has been studied as a first-line treatment for patients with HER2-positive advanced gastric cancer (AGC). The effect of anti-HER2 therapy according to tumor mutational burden (TMB) in HER2-positive AGC remains unclear.MethodsWe performed next-generation sequencing (NGS), including TMB analysis, in 31 HER2-positive AGC patients with trastuzumab plus chemotherapy as first-line therapy for recurrent (n=8) or metastatic (n=23) tumors. The TruSight Oncology 500 Assay from Illumina (San Diego, CA, USA) was used to evaluate TMB.ResultsAmong 31 patients, 30 had tumors with immunohistochemistry (IHC) 3+, and one was IHC 2+ and silver in situ hybridization (SISH) positive. The median age was 57.0 years old (range, 35-76), and the majority had tumors with low TMB (87.1%, n=27/31). Only four (12.9%) had tumors with high TMB. Of these four, three achieved complete response (CR) or partial response (PR) to treatment, and the remaining patient was not evaluable for tumor response. Objective response rate (ORR) to trastuzumab plus chemotherapy showed a favorable trend in patients with high TMB (75.0%, n=3/4) compared to patients with low TMB (59.3%, n=16/27) (P=0.546). The median progression-free survival (PFS) was not reached in the TMB-high group but was 8.0 months (95% CI, 7.6-8.5) in the TMB-low group (P=0.019)ConclusionThe status of TMB could be a novel biomarker in predicting the efficacy of trastuzumab plus chemotherapy in HER2-positive AGCs.Hye Ryeon KimHye Ryeon KimSoomin AhnHyunji JoHongsik KimJoohyun HongJeeyun LeeHo-Yeong LimWon Ki KangSeung Tae KimFrontiers Media S.A.articletrastuzumabadvanced gastric cancerHER2tumor mutational burdenbiomarkerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	trastuzumab advanced gastric cancer HER2 tumor mutational burden biomarker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	trastuzumab advanced gastric cancer HER2 tumor mutational burden biomarker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hye Ryeon Kim Hye Ryeon Kim Soomin Ahn Hyunji Jo Hongsik Kim Joohyun Hong Jeeyun Lee Ho-Yeong Lim Won Ki Kang Seung Tae Kim The Impact of Tumor Mutation Burden on the Effect of Frontline Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric Cancers
description	BackgroundTrastuzumab is a HER2-trargeted humanized monoclonal antibody that has been studied as a first-line treatment for patients with HER2-positive advanced gastric cancer (AGC). The effect of anti-HER2 therapy according to tumor mutational burden (TMB) in HER2-positive AGC remains unclear.MethodsWe performed next-generation sequencing (NGS), including TMB analysis, in 31 HER2-positive AGC patients with trastuzumab plus chemotherapy as first-line therapy for recurrent (n=8) or metastatic (n=23) tumors. The TruSight Oncology 500 Assay from Illumina (San Diego, CA, USA) was used to evaluate TMB.ResultsAmong 31 patients, 30 had tumors with immunohistochemistry (IHC) 3+, and one was IHC 2+ and silver in situ hybridization (SISH) positive. The median age was 57.0 years old (range, 35-76), and the majority had tumors with low TMB (87.1%, n=27/31). Only four (12.9%) had tumors with high TMB. Of these four, three achieved complete response (CR) or partial response (PR) to treatment, and the remaining patient was not evaluable for tumor response. Objective response rate (ORR) to trastuzumab plus chemotherapy showed a favorable trend in patients with high TMB (75.0%, n=3/4) compared to patients with low TMB (59.3%, n=16/27) (P=0.546). The median progression-free survival (PFS) was not reached in the TMB-high group but was 8.0 months (95% CI, 7.6-8.5) in the TMB-low group (P=0.019)ConclusionThe status of TMB could be a novel biomarker in predicting the efficacy of trastuzumab plus chemotherapy in HER2-positive AGCs.
format	article
author	Hye Ryeon Kim Hye Ryeon Kim Soomin Ahn Hyunji Jo Hongsik Kim Joohyun Hong Jeeyun Lee Ho-Yeong Lim Won Ki Kang Seung Tae Kim
author_facet	Hye Ryeon Kim Hye Ryeon Kim Soomin Ahn Hyunji Jo Hongsik Kim Joohyun Hong Jeeyun Lee Ho-Yeong Lim Won Ki Kang Seung Tae Kim
author_sort	Hye Ryeon Kim
title	The Impact of Tumor Mutation Burden on the Effect of Frontline Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric Cancers
title_short	The Impact of Tumor Mutation Burden on the Effect of Frontline Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric Cancers
title_full	The Impact of Tumor Mutation Burden on the Effect of Frontline Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric Cancers
title_fullStr	The Impact of Tumor Mutation Burden on the Effect of Frontline Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric Cancers
title_full_unstemmed	The Impact of Tumor Mutation Burden on the Effect of Frontline Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric Cancers
title_sort	impact of tumor mutation burden on the effect of frontline trastuzumab plus chemotherapy in human epidermal growth factor receptor 2-positive advanced gastric cancers
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3aabafd8b49749279f87e8b796907259
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The Impact of Tumor Mutation Burden on the Effect of Frontline Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric Cancers

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