Trastuzumab deruxtecan for the treatment of metastatic non-small cell lung cancer harboring HER2 non-exon 19/20 mutations: four case reports

BackgroundPatients with human epidermal growth factor receptor 2 (HER2)-mutant non-small cell lung cancer (NSCLC) have poor prognosis. Trastuzumab deruxtecan (T-DXd) is the first targeted therapy approved for the treatment of patients with HER2-mutant metastatic NSCLC, but the evidence in those with...

Full description

Saved in:
Bibliographic Details
Main Authors: Yan Meng, Yanping Du, Xiaolin Liu, Jue Huang, Hanhan Chen, Chunxia He
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1631768/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849391405349208064
author Yan Meng
Yanping Du
Yanping Du
Xiaolin Liu
Jue Huang
Hanhan Chen
Chunxia He
author_facet Yan Meng
Yanping Du
Yanping Du
Xiaolin Liu
Jue Huang
Hanhan Chen
Chunxia He
author_sort Yan Meng
collection DOAJ
description BackgroundPatients with human epidermal growth factor receptor 2 (HER2)-mutant non-small cell lung cancer (NSCLC) have poor prognosis. Trastuzumab deruxtecan (T-DXd) is the first targeted therapy approved for the treatment of patients with HER2-mutant metastatic NSCLC, but the evidence in those with HER2 non-exon 19/20 mutations is scarce.MethodsWe reported treatment information and outcomes of four patients with metastatic NSCLC harboring HER2 non-exon 19/20 mutations who were treated with T-DXd.ResultsAll the four patients had metastatic lung adenocarcinoma and reached partial response to T-DXd treatment. A 57-year-old female patient with HER2 exon 17 V659E mutation received T-DXd as later-line treatment. Treatment was ongoing and the progression-free survival (PFS) had reached 13 months. Three patients received first-line T-DXd treatment. One patient with HER2 exon 3 T126A mutation had disease progression after 16-month treatment. The other two patients (one with HER2 exon 21 H878Y mutation and one with HER2 exon 17 V659E mutation) were continuing T-DXd treatment, both with a PFS of more than 6 months. No interstitial lung disease or grade ≥3 adverse events occurred in these four patients.ConclusionThe potential of T-DXd in patients with metastatic NSCLC harboring HER2 non-exon 19/20 mutations is considerable, which deserves to be validated in large-sample studies.
format Article
id doaj-art-9fa32d78ce094345908e0d8c0accdfa3
institution Kabale University
issn 1664-3224
language English
publishDate 2025-08-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-9fa32d78ce094345908e0d8c0accdfa32025-08-20T03:41:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16317681631768Trastuzumab deruxtecan for the treatment of metastatic non-small cell lung cancer harboring HER2 non-exon 19/20 mutations: four case reportsYan Meng0Yanping Du1Yanping Du2Xiaolin Liu3Jue Huang4Hanhan Chen5Chunxia He6Department of Medical Oncology, 2nd District, Hainan Cancer Hospital, Hainan, ChinaThe School of Clinical Medicine, Fujian Medical University, Fuzhou,, ChinaDepartment of Pulmonary and Critical Care Medicine, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, ChinaGuangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Medical Oncology, 2nd District, Hainan Cancer Hospital, Hainan, ChinaDepartment of Pulmonary and Critical Care Medicine, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, ChinaGuangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, ChinaBackgroundPatients with human epidermal growth factor receptor 2 (HER2)-mutant non-small cell lung cancer (NSCLC) have poor prognosis. Trastuzumab deruxtecan (T-DXd) is the first targeted therapy approved for the treatment of patients with HER2-mutant metastatic NSCLC, but the evidence in those with HER2 non-exon 19/20 mutations is scarce.MethodsWe reported treatment information and outcomes of four patients with metastatic NSCLC harboring HER2 non-exon 19/20 mutations who were treated with T-DXd.ResultsAll the four patients had metastatic lung adenocarcinoma and reached partial response to T-DXd treatment. A 57-year-old female patient with HER2 exon 17 V659E mutation received T-DXd as later-line treatment. Treatment was ongoing and the progression-free survival (PFS) had reached 13 months. Three patients received first-line T-DXd treatment. One patient with HER2 exon 3 T126A mutation had disease progression after 16-month treatment. The other two patients (one with HER2 exon 21 H878Y mutation and one with HER2 exon 17 V659E mutation) were continuing T-DXd treatment, both with a PFS of more than 6 months. No interstitial lung disease or grade ≥3 adverse events occurred in these four patients.ConclusionThe potential of T-DXd in patients with metastatic NSCLC harboring HER2 non-exon 19/20 mutations is considerable, which deserves to be validated in large-sample studies.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1631768/fulltrastuzumab deruxtecannon-small cell lung cancerhuman epidermal growth factor receptor 2mutationcase series
spellingShingle Yan Meng
Yanping Du
Yanping Du
Xiaolin Liu
Jue Huang
Hanhan Chen
Chunxia He
Trastuzumab deruxtecan for the treatment of metastatic non-small cell lung cancer harboring HER2 non-exon 19/20 mutations: four case reports
Frontiers in Immunology
trastuzumab deruxtecan
non-small cell lung cancer
human epidermal growth factor receptor 2
mutation
case series
title Trastuzumab deruxtecan for the treatment of metastatic non-small cell lung cancer harboring HER2 non-exon 19/20 mutations: four case reports
title_full Trastuzumab deruxtecan for the treatment of metastatic non-small cell lung cancer harboring HER2 non-exon 19/20 mutations: four case reports
title_fullStr Trastuzumab deruxtecan for the treatment of metastatic non-small cell lung cancer harboring HER2 non-exon 19/20 mutations: four case reports
title_full_unstemmed Trastuzumab deruxtecan for the treatment of metastatic non-small cell lung cancer harboring HER2 non-exon 19/20 mutations: four case reports
title_short Trastuzumab deruxtecan for the treatment of metastatic non-small cell lung cancer harboring HER2 non-exon 19/20 mutations: four case reports
title_sort trastuzumab deruxtecan for the treatment of metastatic non small cell lung cancer harboring her2 non exon 19 20 mutations four case reports
topic trastuzumab deruxtecan
non-small cell lung cancer
human epidermal growth factor receptor 2
mutation
case series
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1631768/full
work_keys_str_mv AT yanmeng trastuzumabderuxtecanforthetreatmentofmetastaticnonsmallcelllungcancerharboringher2nonexon1920mutationsfourcasereports
AT yanpingdu trastuzumabderuxtecanforthetreatmentofmetastaticnonsmallcelllungcancerharboringher2nonexon1920mutationsfourcasereports
AT yanpingdu trastuzumabderuxtecanforthetreatmentofmetastaticnonsmallcelllungcancerharboringher2nonexon1920mutationsfourcasereports
AT xiaolinliu trastuzumabderuxtecanforthetreatmentofmetastaticnonsmallcelllungcancerharboringher2nonexon1920mutationsfourcasereports
AT juehuang trastuzumabderuxtecanforthetreatmentofmetastaticnonsmallcelllungcancerharboringher2nonexon1920mutationsfourcasereports
AT hanhanchen trastuzumabderuxtecanforthetreatmentofmetastaticnonsmallcelllungcancerharboringher2nonexon1920mutationsfourcasereports
AT chunxiahe trastuzumabderuxtecanforthetreatmentofmetastaticnonsmallcelllungcancerharboringher2nonexon1920mutationsfourcasereports