739P - Comparison of breast and gastric HER2 immunohistochemistry (IHC) scoring criteria in the assessment of endometrial endometrioid adenocarcinoma (EEA)

Background

The DESTINY-PanTumor02 trial demonstrated efficacy of HER2-directed antibody drug conjugates (ADCs) in the treatment of gynecologic malignancies, including EEA. Trial eligibility was determined utilizing HER2 IHC gastric criteria, but many institutions historically use breast criteria for IHC interpretations. As neither scoring system has been validated in gynecologic neoplasms, our study seeks to compare them in EEA.

Methods

Blinded pathology review of HER2 IHC (4B5) from 263 randomly selected EEAs was performed by two board-certified pathologists utilizing gastric and breast criteria. Results of the two scoring systems were compared (Positive [P]: intensity 3+, >10% [breast] or ≥10% [gastric] tumor cell staining, Equivocal [E]: 2+, >10% [breast] or ≥10% [gastric], Low/Negative [N]: >1+, ≤10% [breast] or <10% [gastric], or any percentage of 1+). Tumors were analyzed for ERBB2 copy number amplification by DNA (592-gene or whole exome) sequencing and statistical significance determined using unpaired T-test.

Results

Of HER2 P cases, 96% (49/51) were concordant between breast/gastric criteria, median of 13.0 copies of ERBB2. HER2 E tumors showed a lower rate of concordance with 51% (30/59) concordant cases, median of 2.5 copies of ERBB2. Of discordant HER2 E tumors, 44% (26/59) of E cases were N by breast/E by gastric (1.8 median copies, p < 0.02 vs concordant cases). HER2 N cases were 86% (155/182) concordant (1.9 median copies, p = 0.96 vs N by breast/E by gastric cases).

Conclusions

While gastric and breast criteria demonstrated 96% concordance in identifying EEAs positive for HER2 overexpression, equivocal staining was more often documented with gastric scoring. This greater frequency of equivocal results may suggest a preference for gastric criteria in the assessment of EEA, matching trial inclusion criteria where clinical benefit of HER2 ADCs has been established in patients with HER2 equivocal tumors. Table: 739P

Concordance and discordance of HER2 IHC calls by gastric and breast criteria

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M.G. Evans: Financial Interests, Personal, Invited Speaker: Caris Life Sciences; Financial Interests, Personal, Full or part-time Employment: Caris Life Sciences; Financial Interests, Personal, Stocks/Shares: Caris Life Sciences. H. Krause: Financial Interests, Institutional, Full or part-time Employment, I am a full time employee at Caris Life Sciences: Caris Life Sciences. A. Elliott: Financial Interests, Personal, Full or part-time Employment: Caris Life Sciences. C. Mathews: Financial Interests, Institutional, Research Funding: AstraZeneca, Tesaro/GSK, Astellas Pharma, Seattle Genetics, Deciphera, Moderna, Regeneron, Roche/Genentech, Pfizer, Laekna Therapeutics, EMD Serono, Merck, Genmab, Avenge Bio, Zentalis, ImmunoGen, Elucida Oncology, Artios, Volastra Therapeutics, AADI, Repare Therapeutics. S. Wei: Financial Interests, Personal, Other, board member of molecular tumor board of Caris Life Sciences: Caris Life Sciences. J. Hechtman: Financial Interests, Personal, Full or part-time Employment: Caris Life Sciences; Financial Interests, Personal, Speaker, Consultant, Advisor: Pfizer. D. Bryant: Financial Interests, Institutional, Full or part-time Employment, Senior Medical Director of Pathology: Caris Life Sciences; Financial Interests, Personal, Stocks/Shares, Own stock and have stock options: Caris Life Sciences. M. Oberley: Financial Interests, Personal, Full or part-time Employment: Caris Life Sciences; Financial Interests, Personal, Stocks/Shares: Caris Life Sciences. M.A. Powell: Financial Interests, Personal, Speaker, Consultant, Advisor: GSK, Merck, Eisai, AstraZeneca, Seagen, Immunogenicity. P.H. Thaker: Financial Interests, Personal, Advisory Board: Merck, GSK, Seagen, Immunon, ImmunoGen, Novocure, Zentalis; Financial Interests, Personal, Other, consulting: Caris, Verastem; Financial Interests, Personal, Other, DSMB committee: Iovance; Financial Interests, Institutional, Research Grant: Merck, GSK; Financial Interests, Institutional, Coordinating PI: Zentalis, Seagen, ImmunoGen; Financial Interests, Institutional, Local PI: Verastem, Genelux. All other authors have declared no conflicts of interest.