Case report: Patients with positive HER-2 amplification locally advanced gastroesophageal junction cancer achieved pathologic complete response with the addition of pembrolizumab to chemotherapy plus trastuzumab as neoadjuvant therapy

BackgroundHuman epidermal growth factor receptor 2(HER-2) is the most prominent therapeutic target for gastric (G)/gastroesophageal junction (GEJ) cancer. Guidelines recommend its use for treating G/GEJ cancers. However, targeted therapy did not significantly improve survival outcomes compared to th...

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Main Authors: Huanhuan Li, Chao Ren, Donghai Cui, Tao Wu, Zhiyong Nie
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1555074/full
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author Huanhuan Li
Chao Ren
Donghai Cui
Tao Wu
Zhiyong Nie
author_facet Huanhuan Li
Chao Ren
Donghai Cui
Tao Wu
Zhiyong Nie
author_sort Huanhuan Li
collection DOAJ
description BackgroundHuman epidermal growth factor receptor 2(HER-2) is the most prominent therapeutic target for gastric (G)/gastroesophageal junction (GEJ) cancer. Guidelines recommend its use for treating G/GEJ cancers. However, targeted therapy did not significantly improve survival outcomes compared to those with neoadjuvant therapy. The KEYNOTE-811 trial revealed an improved objective response rate (74% vs. 52%; P=.0001) and median duration of response (10.6 vs 9.5 months) with the addition of pembrolizumab (PD-1) to chemotherapy plus trastuzumab compared to that with the addition of placebo in patients with HER-2 overexpression-positive advanced adenocarcinoma. Therefore, addition of PD-1 to chemotherapy plus trastuzumab may lead to a better response in patients with G/GEJ cancer.Case presentationA 66-year-old man was diagnosed with stage III GEJ adenocarcinoma with celiac lymph node metastasis. Immunohistochemical results indicated HER-2(3+) and PD-L1 CPS=5. The patient received three cycles of pembrolizumab plus trastuzumab and chemotherapy preoperatively and underwent radical surgery on November 22, 2022.ConclusionPatients with HER-2-positive locally advanced GEJ cancers received PD-1 immunotherapy combined with trastuzumab and neoadjuvant chemotherapy and achieved a complete pathological response. Hence, it is a novel, highly specific, and potent therapeutic option for HER-2-positive patients and should henceforth be considered as a new treatment approach.
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spelling doaj-art-226da1c343b64dce93d03bce8c618d7d2025-02-12T07:25:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15550741555074Case report: Patients with positive HER-2 amplification locally advanced gastroesophageal junction cancer achieved pathologic complete response with the addition of pembrolizumab to chemotherapy plus trastuzumab as neoadjuvant therapyHuanhuan LiChao RenDonghai CuiTao WuZhiyong NieBackgroundHuman epidermal growth factor receptor 2(HER-2) is the most prominent therapeutic target for gastric (G)/gastroesophageal junction (GEJ) cancer. Guidelines recommend its use for treating G/GEJ cancers. However, targeted therapy did not significantly improve survival outcomes compared to those with neoadjuvant therapy. The KEYNOTE-811 trial revealed an improved objective response rate (74% vs. 52%; P=.0001) and median duration of response (10.6 vs 9.5 months) with the addition of pembrolizumab (PD-1) to chemotherapy plus trastuzumab compared to that with the addition of placebo in patients with HER-2 overexpression-positive advanced adenocarcinoma. Therefore, addition of PD-1 to chemotherapy plus trastuzumab may lead to a better response in patients with G/GEJ cancer.Case presentationA 66-year-old man was diagnosed with stage III GEJ adenocarcinoma with celiac lymph node metastasis. Immunohistochemical results indicated HER-2(3+) and PD-L1 CPS=5. The patient received three cycles of pembrolizumab plus trastuzumab and chemotherapy preoperatively and underwent radical surgery on November 22, 2022.ConclusionPatients with HER-2-positive locally advanced GEJ cancers received PD-1 immunotherapy combined with trastuzumab and neoadjuvant chemotherapy and achieved a complete pathological response. Hence, it is a novel, highly specific, and potent therapeutic option for HER-2-positive patients and should henceforth be considered as a new treatment approach.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1555074/fullHER-2immunotherapyneoadjuvant therapygastric cancergastroesophageal junction adenocarcinoma
spellingShingle Huanhuan Li
Chao Ren
Donghai Cui
Tao Wu
Zhiyong Nie
Case report: Patients with positive HER-2 amplification locally advanced gastroesophageal junction cancer achieved pathologic complete response with the addition of pembrolizumab to chemotherapy plus trastuzumab as neoadjuvant therapy
Frontiers in Immunology
HER-2
immunotherapy
neoadjuvant therapy
gastric cancer
gastroesophageal junction adenocarcinoma
title Case report: Patients with positive HER-2 amplification locally advanced gastroesophageal junction cancer achieved pathologic complete response with the addition of pembrolizumab to chemotherapy plus trastuzumab as neoadjuvant therapy
title_full Case report: Patients with positive HER-2 amplification locally advanced gastroesophageal junction cancer achieved pathologic complete response with the addition of pembrolizumab to chemotherapy plus trastuzumab as neoadjuvant therapy
title_fullStr Case report: Patients with positive HER-2 amplification locally advanced gastroesophageal junction cancer achieved pathologic complete response with the addition of pembrolizumab to chemotherapy plus trastuzumab as neoadjuvant therapy
title_full_unstemmed Case report: Patients with positive HER-2 amplification locally advanced gastroesophageal junction cancer achieved pathologic complete response with the addition of pembrolizumab to chemotherapy plus trastuzumab as neoadjuvant therapy
title_short Case report: Patients with positive HER-2 amplification locally advanced gastroesophageal junction cancer achieved pathologic complete response with the addition of pembrolizumab to chemotherapy plus trastuzumab as neoadjuvant therapy
title_sort case report patients with positive her 2 amplification locally advanced gastroesophageal junction cancer achieved pathologic complete response with the addition of pembrolizumab to chemotherapy plus trastuzumab as neoadjuvant therapy
topic HER-2
immunotherapy
neoadjuvant therapy
gastric cancer
gastroesophageal junction adenocarcinoma
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1555074/full
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