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Analytical and clinical validation of PATHWAY Anti-HER-2/neu (4B5) antibody to assess HER2-low status for trastuzumab deruxtecan treatment in breast cancer

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Title: Analytical and clinical validation of PATHWAY Anti-HER-2/neu (4B5) antibody to assess HER2-low status for trastuzumab deruxtecan treatment in breast cancer
Authors: Charo Garrido, Melissa Manoogian, Dhiraj Ghambire, Shawn Lucas, Maha Karnoub, Matthew T. Olson, David G. Hicks, Gary Tozbikian, Aleix Prat, Naoto T. Ueno, Shanu Modi, Wenqin Feng, Judith Pugh, Ching Hsu, Junji Tsurutani, David Cameron, Nadia Harbeck, Qijun Fang, Shirin Khambata-Ford, Xuemin Liu, Landon J. Inge, Patrik Vitazka
Source: Virchows Arch
Publisher Information: Springer Science and Business Media LLC, 2023.
Publication Year: 2023
Subject Terms: Immunoconjugates, Female [MeSH], HER2-low, Receptor, ErbB-2/metabolism [MeSH], Humans [MeSH], Breast cancer, Breast Neoplasms/drug therapy [MeSH], Trastuzumab/therapeutic use [MeSH], Breast Neoplasms/metabolism [MeSH], Animals [MeSH], Camptothecin/analogs, Receptor, ErbB-2/analysis [MeSH], Camptothecin/therapeutic use [MeSH], Immunoconjugates/therapeutic use [MeSH], Original Article, Companion diagnostic, Reproducibility of Results [MeSH], Biomarkers, Tumor/metabolism [MeSH], Antineoplastic Agents, Immunological/therapeutic use [MeSH], Antibodies, Monoclonal, Humanized/therapeutic use [MeSH], Biomarkers, Tumor/analysis [MeSH], 4B5, Immunohistochemistry/methods [MeSH], Breast Neoplasms/pathology [MeSH], Receptor, ErbB-2, Reproducibility of Results, Breast Neoplasms, Trastuzumab, Antibodies, Monoclonal, Humanized, Immunohistochemistry, 3. Good health, Antineoplastic Agents, Immunological, Biomarkers, Tumor, Humans, Animals, Female, Camptothecin
Description: In DESTINY-Breast04 (DB-04), safety and efficacy of HER2-targeted antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) in previously treated HER2-low unresectable/metastatic breast cancer were established. This manuscript describes the analytical validation of PATHWAY Anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody (PATHWAY HER2 (4B5)) to assess HER2-low status and its clinical performance in DB-04. Preanalytical processing and tissue staining parameters were evaluated to determine their impact on HER2 scoring. The recommended antibody staining procedure provided the optimal tumor staining, and deviations in cell conditioning and/or antibody incubation times resulted in unacceptable negative control staining and/or HER2-low status changes. Comparisons between antibody lots, kit lots, instruments, and day-to-day runs showed overall percent agreements (OPAs) exceeding 97.9%. Inter-laboratory reproducibility showed OPAs of ≥97.4% for all study endpoints. PATHWAY HER2 (4B5) was utilized in DB-04 for patient selection using 1340 tumor samples (59.0% metastatic, 40.7% primary, (0.3% missing data); 74.3% biopsy, 25.7% resection/excisions). Overall, 77.6% (823/1060) of samples were HER2-low by both central and local testing, with the level of concordance differing by sample region of origin and collection date. In DB-04, the efficacy of T-DXd over chemotherapy of physician’s choice was consistent, regardless of the characteristics of the sample used (primary or metastatic, archival, or newly collected, biopsy or excision/resection). These results demonstrate that PATHWAY HER2 (4B5) is precise and reproducible for scoring HER2-low status and can be used with multiple breast cancer sample types for reliably identifying patients whose tumors have HER2-low expression and are likely to derive clinical benefit from T-DXd.
Document Type: Article
Other literature type
Language: English
ISSN: 1432-2307
0945-6317
DOI: 10.1007/s00428-023-03671-x
Access URL: https://pubmed.ncbi.nlm.nih.gov/37857998
https://repository.publisso.de/resource/frl:6506949
Rights: CC BY
Accession Number: edsair.doi.dedup.....d244f03903e3c4e2d7750cb4b815ad69
Database: OpenAIRE
Description
Abstract:In DESTINY-Breast04 (DB-04), safety and efficacy of HER2-targeted antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) in previously treated HER2-low unresectable/metastatic breast cancer were established. This manuscript describes the analytical validation of PATHWAY Anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody (PATHWAY HER2 (4B5)) to assess HER2-low status and its clinical performance in DB-04. Preanalytical processing and tissue staining parameters were evaluated to determine their impact on HER2 scoring. The recommended antibody staining procedure provided the optimal tumor staining, and deviations in cell conditioning and/or antibody incubation times resulted in unacceptable negative control staining and/or HER2-low status changes. Comparisons between antibody lots, kit lots, instruments, and day-to-day runs showed overall percent agreements (OPAs) exceeding 97.9%. Inter-laboratory reproducibility showed OPAs of ≥97.4% for all study endpoints. PATHWAY HER2 (4B5) was utilized in DB-04 for patient selection using 1340 tumor samples (59.0% metastatic, 40.7% primary, (0.3% missing data); 74.3% biopsy, 25.7% resection/excisions). Overall, 77.6% (823/1060) of samples were HER2-low by both central and local testing, with the level of concordance differing by sample region of origin and collection date. In DB-04, the efficacy of T-DXd over chemotherapy of physician’s choice was consistent, regardless of the characteristics of the sample used (primary or metastatic, archival, or newly collected, biopsy or excision/resection). These results demonstrate that PATHWAY HER2 (4B5) is precise and reproducible for scoring HER2-low status and can be used with multiple breast cancer sample types for reliably identifying patients whose tumors have HER2-low expression and are likely to derive clinical benefit from T-DXd.
ISSN:14322307
09456317
DOI:10.1007/s00428-023-03671-x