TEST:

HER2 IQFISH pharmDx

A significant proportion of previous 'HER2-negative' primaries and DM cases were reclassified as HER2-low. Discordant HER2 status between IBC primary and metastasis and between different DM sites demonstrated tumour heterogeneity and highlights the need for HER2 retesting in distant metastasis.

By using USC-specific IHC scoring criteria, both HercepTest and 4B5 assays showed high specificities (100%) for HER2 gene amplification in IHC 3+ cases, high IHC/FISH concordance, and comparable sensitivity for detecting HER2 gene amplification. The notable false negative rates using IHC 2+ as a cut-off for reflexing FISH analysis may warrant consideration for performing FISH in IHC 1+ cases until more data become available.

Significant proportion of previous "HER2 negative" primaries and DM cases are reclassified as HER2 low. Discordant HER2 status between IBC primary and metastasis and between different DM sites demonstrated tumor heterogeneity and highlights the need for HER2 retesting in distant metastasis.

To our knowledge, this study is the first to compare the performance of the two most commonly-used HER2 IHC methods to HER2 gene amplification by FISH. Both HercepTest and 4B5 HER2 IHC had 100% specificity for detecting HER2 gene amplification in USC, while HercepTest has superior sensitivity. Therapeutic targeting of HER2 is among the most significant advancements in this disease in decades, specifically for patients with HER2 positive advanced stage and recurrent USC.

In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201)... The HORIZON III trial (NCT00384176) evaluated FOLFOX + bevacizumab or cediranib (AZD2171) as first-line (1L) treatment in patients with metastatic CRC (Schmoll J Clin Oncol 2012)... This exploratory analysis of the HORIZON III study provides insights into HER2 prevalence in 1L, unselected, advanced/metastatic CRC, finding that 2.1% of tumors were HER2 positive. The demographic characteristics of patients with analyzable samples were representative of the entire HORIZON III study population; however, further assessment of KRAS status and other clinicopathological characteristics is needed. These data may inform future clinical development and support selection of patients with CRC who are likely to benefit from HER2 targeting therapies.

Background Conventional pathologic scoring of HER2 by IHC is proven to distinguish potential responders to trastuzumab but has not been effective for next generation antibody drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd), which is capable of bystander killing...Further clinical verification and validation on large cohorts is needed. Footnote: This study was approved by the IRB at MSKCC.