Trastuzumab Deruxtecan-Induced Interstitial Lung Disease/Pneumonitis in ERBB2-Positive Advanced Solid Malignancies: A Systematic Review.


Journal

Drugs
ISSN: 1179-1950
Titre abrégé: Drugs
Pays: New Zealand
ID NLM: 7600076

Informations de publication

Date de publication:
Jun 2022
Historique:
accepted: 23 05 2022
pubmed: 28 6 2022
medline: 15 7 2022
entrez: 27 6 2022
Statut: ppublish

Résumé

Trastuzumab deruxtecan (T-DXd) is a novel anti-ERBB2 antibody drug conjugate that appears to be associated with an increased risk of lung toxicity. We performed a systematic review to describe the incidence, severity, and management of T-DXd-induced interstitial lung disease (ILD) or pneumonitis. We searched PubMed/MEDLINE, Embase, Cochrane, and Web of Sciences through to 1 January, 2022, for human clinical trials that assessed T-DXd in adults with ERBB2-positive advanced solid tumors and described the rate of ILD/pneumonitis. Study screening was performed by two researchers. Data were extracted from the full-text articles. Fourteen studies with a total of 1193 patients with different types of advanced solid malignancies were included in our systematic review. The overall incidence of all-grade ILD/pneumonitis cases that were adjudicated by an independent committee was 11.40% (ILD/pneumonitis cases, n = 136 out of total n = 1193). Grading of the adjudicated T-DXd-induced ILD/pneumonitis was reported in 122 patients with the majority of the cases (78.69%, n = 96) occurring as grade 1 or 2. Death was reported in 13 out of 122 (10.66%) patients. The highest incidence of ILD/pneumonitis was seen in patients with uterine carcinomatosis (26.47%) and non-small cell lung cancer (24.77%). Interstitial lung disease/pneumonitis events were treated with a dose interruption or reduction, treatment discontinuation, corticosteroids, and supportive care. Interstitial lung disease/pneumonitis is a well-described, serious, and potentially life-threatening adverse event that is associated with T-DXd. Further studies are needed to identify the risk factors and the underlying pathophysiology of T-DXd-induced ILD/pneumonitis to prevent occurrence and to develop effective management strategies.

Sections du résumé

BACKGROUND AND OBJECTIVE OBJECTIVE
Trastuzumab deruxtecan (T-DXd) is a novel anti-ERBB2 antibody drug conjugate that appears to be associated with an increased risk of lung toxicity. We performed a systematic review to describe the incidence, severity, and management of T-DXd-induced interstitial lung disease (ILD) or pneumonitis.
METHODS METHODS
We searched PubMed/MEDLINE, Embase, Cochrane, and Web of Sciences through to 1 January, 2022, for human clinical trials that assessed T-DXd in adults with ERBB2-positive advanced solid tumors and described the rate of ILD/pneumonitis. Study screening was performed by two researchers. Data were extracted from the full-text articles.
RESULTS RESULTS
Fourteen studies with a total of 1193 patients with different types of advanced solid malignancies were included in our systematic review. The overall incidence of all-grade ILD/pneumonitis cases that were adjudicated by an independent committee was 11.40% (ILD/pneumonitis cases, n = 136 out of total n = 1193). Grading of the adjudicated T-DXd-induced ILD/pneumonitis was reported in 122 patients with the majority of the cases (78.69%, n = 96) occurring as grade 1 or 2. Death was reported in 13 out of 122 (10.66%) patients. The highest incidence of ILD/pneumonitis was seen in patients with uterine carcinomatosis (26.47%) and non-small cell lung cancer (24.77%). Interstitial lung disease/pneumonitis events were treated with a dose interruption or reduction, treatment discontinuation, corticosteroids, and supportive care.
CONCLUSIONS CONCLUSIONS
Interstitial lung disease/pneumonitis is a well-described, serious, and potentially life-threatening adverse event that is associated with T-DXd. Further studies are needed to identify the risk factors and the underlying pathophysiology of T-DXd-induced ILD/pneumonitis to prevent occurrence and to develop effective management strategies.

Identifiants

pubmed: 35759121
doi: 10.1007/s40265-022-01736-w
pii: 10.1007/s40265-022-01736-w
pmc: PMC9276583
doi:

Substances chimiques

Immunoconjugates 0
trastuzumab deruxtecan 5384HK7574
ERBB2 protein, human EC 2.7.10.1
Receptor, ErbB-2 EC 2.7.10.1
Trastuzumab P188ANX8CK
Camptothecin XT3Z54Z28A

Types de publication

Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

979-987

Informations de copyright

© 2022. The Author(s).

Références

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Auteurs

Ziad Abuhelwa (Z)

Department of Internal Medicine, University of Toledo, Toledo, OH, USA.

Abdurahman Alloghbi (A)

Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Cancer Research Unit and Department of Oncology, King Khalid University, Abha, Saudi Arabia.

Ali Alqahtani (A)

Department of Oncology, Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington, DC, USA.

Misako Nagasaka (M)

Department of Medicine, University of California Irvine School of Medicine, 101 The City Drive South, Building 200, Room 410, ZOT 4061, Orange, CA, 92868, USA. nagasakm@hs.uci.edu.
Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Japan. nagasakm@hs.uci.edu.

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Classifications MeSH