Neoadjuvant Afatinib for stage III EGFR-mutant non-small cell lung cancer: a phase II study.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 08 2023
03 08 2023
Historique:
received:
16
12
2022
accepted:
25
07
2023
medline:
7
8
2023
pubmed:
4
8
2023
entrez:
3
8
2023
Statut:
epublish
Résumé
Afatinib, an irreversible ErbB-family blocker, could improve the survival of advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer patients (NSCLCm+). This phase II trial (NCT04201756) aimed to assess the feasibility of neoadjuvant Afatinib treatment for stage III NSCLCm+. Forty-seven patients received neoadjuvant Afatinib treatment (40 mg daily). The primary endpoint was objective response rate (ORR). Secondary endpoints included pathological complete response (pCR) rate, pathological downstaging rate, margin-free resection (R0) rate, event-free survival, disease-free survival, progression-free survival, overall survival, treatment-related adverse events (TRAEs). The ORR was 70.2% (95% CI: 56.5% to 84.0%), meeting the pre-specified endpoint. The major pathological response (MPR), pCR, pathological downstaging, and R0 rates were 9.1%, 3.0%, 57.6%, and 87.9%, respectively. The median survivals were not reached. The most common TRAEs were diarrhea (78.7%) and rash (78.7%). Only three patients experienced grade 3/4 TRAEs. Biomarker analysis and tumor microenvironment dynamics by bulk RNA sequencing were included as predefined exploratory endpoints. CISH expression was a promising marker for Afatinib response (AUC = 0.918). In responders, compared to baseline samples, increasing T-cell- and B-cell-related features were observed in post-treatment tumor and lymph-node samples, respectively. Neoadjuvant Afatinib is feasible for stage III NSCLC+ patients and leads to dynamic changes in the tumor microenvironment.
Identifiants
pubmed: 37537219
doi: 10.1038/s41467-023-40349-z
pii: 10.1038/s41467-023-40349-z
pmc: PMC10400609
doi:
Substances chimiques
Afatinib
41UD74L59M
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Protein Kinase Inhibitors
0
Banques de données
ClinicalTrials.gov
['NCT04201756']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4655Informations de copyright
© 2023. The Author(s).
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