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Genomic signatures define three subtypes of EGFR-mutant stage II–III non-small-cell lung cancer with distinct adjuvant therapy outcomes
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Genomic signatures define three subtypes of EGFR-mutant stage II–III non-small-cell lung cancer with distinct adjuvant therapy outcomes
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Journal Article
Genomic signatures define three subtypes of EGFR-mutant stage II–III non-small-cell lung cancer with distinct adjuvant therapy outcomes
2021
Overview
The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected
EGFR
-mutant stage II–IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (
TP53
exon4/5 mutations,
RB1
alterations, and copy number gains of
NKX2-1
,
CDK4
, and
MYC
). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected
EGFR
-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.
Adjuvant gefitinib improves outcomes in non-small cell lung cancer (NSCLC) patients compared to chemotherapy, but not in all cases. Here, the authors find genomic biomarkers of response to gefitinib in NSCLC patients from the ADJUVANT trial, and propose a score to stratify them by potential benefit from the treatment.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Biomarkers, Tumor - genetics
/ Carcinoma, Non-Small-Cell Lung - drug therapy
/ Carcinoma, Non-Small-Cell Lung - genetics
/ Epidermal growth factor receptors
/ Genomics
/ Humanities and Social Sciences
/ Humans
/ Kinases
/ Lung Neoplasms - drug therapy
/ Mutants
/ Mutation
/ Non-small cell lung carcinoma
/ Patients
/ Science
/ Survival
/ Thyroid transcription factor 1
/ Tumors
/ Tyrosine
