Abstract 172P
Background
On April 5, 2024, FDA granted accelerated approval to T-Dxd for adult patients with metastatic HER2-positive Immunohistochemistry (IHC) 3+ relapsed/refractory solid tumors. However, the real-world expression of HER2 across solid tumors and its implications in clinical practice are unknown.
Methods
Solid tumor specimens from UAB sent to Caris Life Sciences were analyzed for HER2 status. HER2 (ERBB2) copy number amplification (amp) was determined by comparing sample's average depth and sequencing depth of each exon to a pre-calibrated reference. Copy number (CN) > 6 was classified as positive, while CN ≥ 6 with low statistical confidence was labeled as intermediate. HER2 variants (SNV/INDELs) were categorized based on ACMG standards. IHC assays were performed using FDA-approved companion diagnostic tests: HER2/neu (PATHWAY anti-HER-2/neu (4B5), Ventana). IHC results adhere to ASCO/CAP scoring criteria: 0 (no expression), 1+, 2+, or 3. Data from these test reports were extracted and analyzed using descriptive statistics.
Results
We analyzed 653 cases across 24 cancer types: colorectal carcinoma (30.3%, n=198), uterine neoplasms (21.3%, n=139), metastatic breast carcinoma (10.1%, n=66), cholangiocarcinoma (8.6%, n=56) & ovarian/fallopian carcinomas (6.9%, n=45). Tumors with highest proportion of HER2 IHC 3+ in our cohort were salivary gland tumors (16.7%, n=1), esophageal/esophagogastric junction carcinoma (10.3%, n=3), breast carcinoma (9.1%, n=6), ovarian/fallopian carcinomas (6.7%, n=3) & cholangiocarcinoma (3.6%, n=2). HER2 IHC scores were 3.1% IHC 3+ (n=20), 13.2% IHC 2+ (n=86) & 19.8% IHC 1+ (n=129). CNV analysis revealed 3.1% (n=20) with positive amp & 3.5% (n=23) intermediate. Moreover, 3.1% (n=20) harbored pathogenic HER2 mutations. HER2 amp & overexpression varied notably among tumor types. In the positive CNV amp cohort, 75% showed IHC 3+ status, whereas, only 8.7% in the intermediate group. Interestingly, in cases with pathogenic HER2 mutations, only 5% had IHC 3+.
Conclusions
Our study highlights the variable expression and significance of HER2 testing across multiple solid tumor types, reinforcing the importance of HER2 testing to optimize the utilization of T-Dxd in the real-world setting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Desai: Financial Interests, Personal, Advisory Board: Sanofi, Amgen, AstraZeneca, Janssen, Foundation Medicine. All other authors have declared no conflicts of interest.
Resources from the same session
102P - Dynamic profiling of ctDNA in HER2-alterated advanced NSCLC treated with pyrotinib and apatinib: Exploratory biomarker analysis from a phase II trial
Presenter: Yucheng Dong
Session: Poster session 08
103P - Epigenetic regulated genes enhanced fragmentomics-based model for early-stage lung cancer detection
Presenter: Yadong Wang
Session: Poster session 08
104P - The development of a classifier of somatic copy number alteration burden in liquid biopsy with potential clinical impact in advanced non-small cell lung cancer (NSCLC)
Presenter: Laura Bonanno
Session: Poster session 08
105P - Plasma ctDNA dynamics as clinical response biomarker for NSCLC: A systematic review and meta-analysis
Presenter: Luís Leite
Session: Poster session 08
106P - Longitudinal molecular characterization in plasma of EGFR mutant non-small cell lung cancer (NSCLC) experiencing early progression (EPD) on first-line osimertinib (Osi)
Presenter: Laura Bonanno
Session: Poster session 08
107P - Germline pathogenic variants identified in tissue- and blood-based whole exome sequencing in advanced solid tumors
Presenter: Takeshi Kuwata
Session: Poster session 08
108P - Assessing molecular characteristics in a large cohort of anal squamous cell carcinoma patients
Presenter: Cristina Smolenschi
Session: Poster session 08
109P - Development and validation of a digital PCR assay for detection and monitoring of universally methylated circulating tumor DNA in patients with high-grade sarcoma
Presenter: Elisabeth Ashton
Session: Poster session 08
110P - 13-plex non-invasive genotyping in HPV related cancers in the MOSCATO trial
Presenter: Elise Rupp
Session: Poster session 08
111P - Leveraging circulating tumor DNA sequencing for first-line cancer treatment: Insights from two prospective precision medicine studies
Presenter: Veronique Debien
Session: Poster session 08