Local HER2 IHC0 is often HER2-low or -ultralow

In a post-hoc analysis of the DESTINY-Breast06 trial, more than half of HR+ breast tumours that locally scored HER2 IHC0 were found to be HER2-low (IHC1+ or IHC2+) or HER2-ultralow (IHC0 with membrane staining) in central testing.

Recently, the phase 3 DESTINY-Breast06 trial (NCT04494425) showed that second- or later-line treatment with trastuzumab deruxtecan (T-DXd) resulted in longer progression-free survival (PFS) than chemotherapy also in patients with HR+ HER2-low or HER2-ultralow metastatic breast cancer [1].

In the trial, HER2 expression was tested both locally and centrally in 1,629 tumour samples, allowing comparison of the local and central test results. Prof. Giuseppe Viale (University of Milan, Italy) presented the results [2].

Central tests found a rate of 12% scoring IHC0 with absent membrane staining, 21% was HER2-ultralow, and 67% was HER2-low. Of tumours that scored HER2 IHC0 locally, 35% were centrally determined as IHC0, 40% as HER2-ultralow, and 24% as HER2-low.

A PFS benefit with T-DXd was consistently observed across subgroups, stratified by either HER2 IHC score, sample type (biopsy vs excision), or tumour location (primary vs metastatic).

Based on this analysis, Prof. Viale concluded that “patients who are likely to benefit from T-DXd could be identified regardless of sample type and location. A majority of patients with a local HER2 IHC0 score were HER2-low or HER2-ultralow with central testing. Therefore, it may be advisable for patients with HER2 IHC0 scores to be reassessed centrally, to determine if they may be eligible for treatment with T-DXd.”

1. Bardia A, et al. N Engl J Med 2024;Sept 14. DOI: 10.1056/NEJMoa2407086.
2. Viale G, et al. Human epidermal growth factor receptor 2 (HER2)-low and HER2-ultralow status determination in tumors of patients (pts) with hormone receptor-positive (HR+) metastatic breast cancer (mBC) in DESTINY-Breast06 (DB-06). Abstract LBA21, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

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Posted on 4 November 2024