Abstract 55P
Background
The binary classification of human epidermal growth factor receptor 2 (HER2) has been reassessed following recent clinical trials, which show promising efficacy in patients with HER2-low [immunohistochemistry (IHC) 1+ or 2+/in situ hybridization (ISH)-] unresectable/metastatic breast cancer (mBC) using a novel anti-HER2 antibody-drug conjugate—trastuzumab deruxtecan (T-DXd). The evidence highlights the need for more granularity in HER2 classification. However, little is known about the prevalence and outcomes of HER2-low mBC in Taiwan.
Methods
This retrospective study rescored the HER2 IHC slides of patients with HER2-negative (IHC 0, 1+, or 2+/ISH-) unresectable/mBC diagnosed from 2017 to 2020. HER2-low prevalence in HER2-negative unresectable/mBC and the agreement between historical scores and rescores were assessed. Clinicopathological characteristics, treatments, and outcomes of patients with HER2-low unresectable/mBC were examined.
Results
Of the rescored HER2-negative cohort, HER2-low prevalence was 61.2% (186/304) and slightly higher in samples tested by non-Ventana 4B5 (vs. Ventana 4B5) assay and obtained from metastatic sites (vs. primary tumors). A high overall percentage agreement between historical and rescored IHC was observed (90.1%;) regardless of IHC assays. The time to next treatment (TTNT) and overall survival (OS) since the initiation of first-line systematic therapy in mBC were numerically longer in the HR+/HER2-low (N = 138) compared to HR-/HER2-low (N = 48) cohorts (median TTNT: 7.6 vs. 4.8 months; median OS: 37.7 vs. 18.8 months). In HR+/HER2-low patients, endocrine therapies were frequent in the first- and second-line treatment, with chemotherapy being more common in the third-line treatment and beyond. Conversely, chemotherapy was predominant in HR-/HER2-low patients.
Conclusions
This study, per the rescored HER2 IHC, suggests that up to two-thirds of HER2-negative unresectable/mBC patients in Taiwan were HER2-low and may benefit from T-DXd. Findings indicate that re-evaluating the HER2 status of HER2-negative patients may enhance treatment approaches with the evolving HER2 classification paradigm.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Daiichi Sankyo Taiwan Ltd.
Funding
Daiichi Sankyo Taiwan Ltd., and AstraZeneca Taiwan Ltd.
Disclosure
W.C. Yang, Y. Huang, C. Huang, Y. Lin: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo Taiwan. All other authors have declared no conflicts of interest.