Giuseppe Viale, MD, University of Milan, Italy, discusses results from a comparison study which found that reassessing local and central immunostaining results within the DESTINY-Breast06 trial identified more patients with HER2-low or HER2-ultralow expression who can be treated with trastuzumab deruxtecan. 

Dr Viale presented these results at the 2024 European Society of Medical Oncology (ESMO) Congress in Barcelona, Spain. 

Transcript: 

I am Giuseppe Viale, I'm professor of pathology and Chairman of the Department of Pathology/Laboratory Medicine at the European Institute of Oncology in Milano, Italy. At this ESMO Congress I presented data on the assessment of the HER2-low and HER2-ultralow status in samples of tumors of the patients that have been enrolled in the DESTINY-Breast06 (DB-06) trial. 

Altogether, HER2-low and ultralow, ultralow is defined by a tumor with 10% or less of tumor cells that are immunoreactive for HER2, so altogether HER2-low and ultralow represents some 85% of all the hormone receptor-positive, HER2-negative metastatic breast cancer. This is the population of patients that has been enrolled in the DESTINY-Breast06 trial. 

Eligibility of the patients to the study was based on the central assessment of HER2, but for more than 1600 of the samples that were submitted for central review, we had both the local and the central assessment, thus enabling us to perform a comparison of the test results between local and central. It was very interesting that of the cases that were locally considered HER2-low, the vast majority, 94% of these cases, were actually confirmed HER2-low or HER2-ultralow by central testing. 

If we look into the HER2-low diagnosis, the percent positive agreement between local and central assessment was 77.8%, which is not bad, but certainly it can be improved via education and training of the pathologists. We were not able to assess the comparison between local and central assessment for HER2-ultralow and the reason is that the central testing was able to identify these tumors, but the local centers, they were not supposed to distinguish within the 0 scores, those cases with or without membrane staining. 

If we look into the cases that were locally considered with a score 0 at the central examination, 40% of these tumors actually were considered HER2-ultralow and 24% were considered HER2-low, so altogether 64% of the samples considered HER20 locally actually had some membrane staining, qualifying for HER-ultralow or HER2-low. 

What we know looking at the results of the DB-06 clinical trial is that trastuzumab deruxtecan, T-DXd, is almost equally effective in patients with tumors expressing HER2 as a low or ultralow expression, so it is important for us to identify in the population of patients whose tumors have been scored as a 0 to reassess, to reevaluate the immunostaining results in order to identify those possibly 64% of cases that actually have some expression of HER2 and therefore maybe eligible for T-DXd treatment. This is the main message of what I have presented at the ESMO Congress today.

Source: 

Salgado RF, Bardia A, Curigliano 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). Presented at 2024 ESMO Congress. September 13-17, 2024. Abstract LBA21