WCLC 2025 - Posters & ePosters-P2.06.96 Exploration the Heterogeneity of HER2 Expression in Potential Candidates for Antibody-Drug Conjugate in Non-Small Cell Lung Cancer

P2.06.96 Exploration the Heterogeneity of HER2 Expression in Potential Candidates for Antibody-Drug Conjugate in Non-Small Cell Lung Cancer

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This study by Dongmei Lin from Peking University Cancer Hospital investigates the heterogeneity of HER2 expression in non-small cell lung cancer (NSCLC), focusing on its impact on antibody-drug conjugate (ADC) treatment candidacy. HER2 alterations—including mutations (2%-4%), amplification (1.7%), and overexpression (15.4%)—are linked to poor NSCLC prognosis. Notably, HER2 mutation shows an objective response rate (ORR) of 54.9% with median progression-free survival (mPFS) of 8.2 months, while HER2 overexpression has a lower ORR of 24.5% and mPFS of 5.4 months. In Chinese populations, HER2 mutation responses appear higher (ORR 58%).<br /><br />In April 2024, the FDA approved trastuzumab deruxtecan (T-DXd) for unresectable/metastatic HER2-positive (IHC 3+) solid tumors with prior treatment failure, underscoring HER2 as a therapeutic target. However, intratumoral heterogeneity of HER2 expression—the spatial and temporal variability within tumors—limits response to HER2-targeted therapies.<br /><br />This study aimed to evaluate spatial heterogeneity of HER2 overexpression in NSCLC, comparing HER2 levels between primary tumors and metastatic lesions, and between biopsy and surgical resection specimens. It also assessed the impact of different HER2 interpretation criteria (gastric vs. breast cancer standards).<br /><br />Using NSCLC samples collected from 2015-2024 with matched resection vs. biopsy and primary vs. metastatic specimens, two pathologists reevaluated cases per gastric cancer HER2 criteria. Findings showed significant heterogeneity, with biopsy and metastatic samples often underestimating HER2 expression compared to resection and primary samples. Expression patterns varied between mosaic and clustered within samples.<br /><br />Clinically, these results suggest that biopsy and metastatic sampling may not fully reveal HER2 status, potentially influencing treatment decisions, particularly for ADC eligibility. Therefore, selecting appropriate tissue samples for HER2 testing is critical to optimizing targeted therapy strategies in NSCLC.

Asset Subtitle

Dongmei Lin

Meta Tag

Speaker Dongmei Lin

Topic Pathology and Biomarkers

Keywords

HER2 expression

non-small cell lung cancer

NSCLC heterogeneity

antibody-drug conjugate

ADC treatment

HER2 mutation

trastuzumab deruxtecan

T-DXd approval

intratumoral heterogeneity

biopsy vs resection