In era of immunotherapy: the value of trastuzumab beyond progression in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer

Background: For patients with human epidermal growth factor receptor-2 (HER2)-positive advanced or metastatic gastric cancer who have progressed on first-line trastuzumab therapy, the clinical value of the continuous use of trastuzumab beyond progression (TBP) is controversial. Objectives: The prese...

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Main Authors: Hui Wang, Caiyun Nie, Weifeng Xu, Jing Li, He Gou, Huifang Lv, Beibei Chen, Jianzheng Wang, Yingjun Liu, Yunduan He, Jing Zhao, Xiaobing Chen
格式: 文件
语言:English
出版: SAGE Publishing 2024-04-01
丛编:Therapeutic Advances in Gastroenterology
在线阅读:https://doi.org/10.1177/17562848241245455
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author Hui Wang
Caiyun Nie
Weifeng Xu
Jing Li
He Gou
Huifang Lv
Beibei Chen
Jianzheng Wang
Yingjun Liu
Yunduan He
Jing Zhao
Xiaobing Chen
author_facet Hui Wang
Caiyun Nie
Weifeng Xu
Jing Li
He Gou
Huifang Lv
Beibei Chen
Jianzheng Wang
Yingjun Liu
Yunduan He
Jing Zhao
Xiaobing Chen
author_sort Hui Wang
collection DOAJ
description Background: For patients with human epidermal growth factor receptor-2 (HER2)-positive advanced or metastatic gastric cancer who have progressed on first-line trastuzumab therapy, the clinical value of the continuous use of trastuzumab beyond progression (TBP) is controversial. Objectives: The present study was conducted to evaluate the efficacy and explore new treatment strategies of TBP for patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer in the era of cancer immunotherapy. Design: Retrospective analysis. Methods: Patients with HER2-positive advanced or metastatic gastric cancer who have failed first-line treatment based on trastuzumab-targeted therapy from June 2019 to December 2020 were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Survival curves of patients were estimated by the Kaplan–Meier method and compared using the log-rank test. Results: In all, 30 patients received TBP with chemotherapy, immunotherapy, or anti-angiogenic therapy, and the other 26 patients received treatment of physician’s choice without trastuzumab. The median PFS in the TBP and non-TBP population was 6.0 [95% confidence interval (CI) = 3.8–8.2] and 3.5 (95% CI = 2.2–4.8) months, respectively ( p  = 0.038), and the median OS was 12.3 (95% CI = 10.4–14.2) and 9.0 (95% CI = 6.6–11.4) months ( p  = 0.008). The patients who received TBP treatment had more favorable PFS and OS than the non-TBP population. In the TBP group, patients who received trastuzumab plus chemotherapy and immunotherapy had higher ORR (40.0% versus 16.7%), DCR (90.0% versus 50.0%), and showed a significant improvement in PFS (7.0 versus 1.9 m) compared to TBP with chemotherapy alone. Subgroup analysis suggested that patients with male, HER2 positive with immunohistochemistry score 3+ and PFS of first-line treatment less than 6 months had a greater benefit from TBP. The incidence of Grade 3–4 adverse events in the TBP and non-TBP groups was 43.3% and 38.5%. Conclusion: The continuous use of TBP improves PFS and OS in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer with well-tolerated toxicity. In the era of immunotherapy, TBP combined with chemotherapy and immunotherapy may further enhance the clinical benefit and provide a new treatment strategy. Trial registration: This study is a retrospective study, which does not require clinical registration.
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spelling doaj.art-eb461969120c41c78b75358b50e2f1a62024-04-12T12:04:21ZengSAGE PublishingTherapeutic Advances in Gastroenterology1756-28482024-04-011710.1177/17562848241245455In era of immunotherapy: the value of trastuzumab beyond progression in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancerHui WangCaiyun NieWeifeng XuJing LiHe GouHuifang LvBeibei ChenJianzheng WangYingjun LiuYunduan HeJing ZhaoXiaobing ChenBackground: For patients with human epidermal growth factor receptor-2 (HER2)-positive advanced or metastatic gastric cancer who have progressed on first-line trastuzumab therapy, the clinical value of the continuous use of trastuzumab beyond progression (TBP) is controversial. Objectives: The present study was conducted to evaluate the efficacy and explore new treatment strategies of TBP for patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer in the era of cancer immunotherapy. Design: Retrospective analysis. Methods: Patients with HER2-positive advanced or metastatic gastric cancer who have failed first-line treatment based on trastuzumab-targeted therapy from June 2019 to December 2020 were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Survival curves of patients were estimated by the Kaplan–Meier method and compared using the log-rank test. Results: In all, 30 patients received TBP with chemotherapy, immunotherapy, or anti-angiogenic therapy, and the other 26 patients received treatment of physician’s choice without trastuzumab. The median PFS in the TBP and non-TBP population was 6.0 [95% confidence interval (CI) = 3.8–8.2] and 3.5 (95% CI = 2.2–4.8) months, respectively ( p  = 0.038), and the median OS was 12.3 (95% CI = 10.4–14.2) and 9.0 (95% CI = 6.6–11.4) months ( p  = 0.008). The patients who received TBP treatment had more favorable PFS and OS than the non-TBP population. In the TBP group, patients who received trastuzumab plus chemotherapy and immunotherapy had higher ORR (40.0% versus 16.7%), DCR (90.0% versus 50.0%), and showed a significant improvement in PFS (7.0 versus 1.9 m) compared to TBP with chemotherapy alone. Subgroup analysis suggested that patients with male, HER2 positive with immunohistochemistry score 3+ and PFS of first-line treatment less than 6 months had a greater benefit from TBP. The incidence of Grade 3–4 adverse events in the TBP and non-TBP groups was 43.3% and 38.5%. Conclusion: The continuous use of TBP improves PFS and OS in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer with well-tolerated toxicity. In the era of immunotherapy, TBP combined with chemotherapy and immunotherapy may further enhance the clinical benefit and provide a new treatment strategy. Trial registration: This study is a retrospective study, which does not require clinical registration.https://doi.org/10.1177/17562848241245455
spellingShingle Hui Wang
Caiyun Nie
Weifeng Xu
Jing Li
He Gou
Huifang Lv
Beibei Chen
Jianzheng Wang
Yingjun Liu
Yunduan He
Jing Zhao
Xiaobing Chen
In era of immunotherapy: the value of trastuzumab beyond progression in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer
Therapeutic Advances in Gastroenterology
title In era of immunotherapy: the value of trastuzumab beyond progression in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer
title_full In era of immunotherapy: the value of trastuzumab beyond progression in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer
title_fullStr In era of immunotherapy: the value of trastuzumab beyond progression in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer
title_full_unstemmed In era of immunotherapy: the value of trastuzumab beyond progression in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer
title_short In era of immunotherapy: the value of trastuzumab beyond progression in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer
title_sort in era of immunotherapy the value of trastuzumab beyond progression in patients with trastuzumab resistant her2 positive advanced or metastatic gastric cancer
url https://doi.org/10.1177/17562848241245455
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