Aditya Bardia, MD, MPH, FASCO, professor, Division of Medication, Division of Hematology/Oncology, Director of Translational Analysis Integration, the College of California, Los Angeles (UCLA) Jonsson Complete Most cancers Heart, UCLA Well being, discusses the necessity for expanded HER2 testing assays for sufferers with HER2-low and -ultralow metastatic breast most cancers.
Present HER2 immunochemistry (IHC) assays have been initially designed to establish excessive ranges of HER2 expression and weren’t supposed to detect low HER2 expression in sufferers with breast most cancers, Bardia begins. Regardless of this limitation, research involving fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) have proven efficacy even in tumors with low HER2 expression per IHC testing, Bardia experiences. As an illustration, the part 3 DESTINY-Breast06 trial (NCT04494425) included sufferers with hormone receptor–optimistic breast most cancers that was both HER2-low or -ultralow, he explains.
On the 2024 ASCO Annual Assembly, outcomes from the first evaluation of the randomized, multicenter, open-label confirmed that therapy with T-DXd led to a statistically vital and clinically significant enchancment in progression-free survival (PFS) in contrast with chemotherapy alone in pretreated sufferers with hormone receptor–optimistic, HER2-low and -ultralow metastatic breast most cancers. Notably, sufferers with HER2-low illness (n = 359) skilled a median PFS of 13.2 months when handled with the investigational agent in contrast with 8.1 months for these given investigator’s alternative of chemotherapy (n = 354; HR, 0.62; 95% CI, 0.51-0.74; P < .0001). Within the intention-to-treat (ITT) inhabitants comprised of sufferers with HER2-low and -ultralow illness, the median PFS was 13.2 months for T-DXd (n = 436) vs 8.1 months for chemotherapy (n = 430; HR, 0.63; 95% CI, 0.53-0.75; P <.0001). An exploratory evaluation confirmed that in sufferers with HER2-ultralow illness, T-DXd (n = 76) generated a median PFS of 13.2 months vs 8.3 months for chemotherapy (n = 76; HR, 0.78; 95% CI, 0.50-1.21).
Though the HER2 IHC assay has been efficient in figuring out excessive HER2 expression, the restrictions in detecting low HER2 expression spotlight the necessity for improved diagnostic instruments, Bardia emphasizes. This raises the query of whether or not oncologists want higher assays, as the present HER2 IHC assay is insufficient for figuring out low-expressing tumors, he concludes.
