Are there differences in T-DXd efficacy along the spectrum of HER2 IHC expression to impact treatment decisions or sequencing?

There do not appear to be differences in T-DXd efficacy along the spectrum of HER2 expression in these low HER2-expressing tumors as seen in Figure S2 and Figure S4. Reviewing the waterfall plot (Fig Supp 4), we see complete responses in approximately as many patients with IHC 1+ as those with IHC 2...

As noted previously, responses to trastuzumab deruxtecan have been observed even among patients with HER2 IHC scores of 0 (Dieras et al., SABCS 2021; Abstract PD8-02.), though response rates were higher when HER2 expression was detectable by IHC. Interestingly, in DESTINY-Breast04 there was no evide...

In the DESTINY-Breast04 trial, similar efficacy was observed for those with 2+ and 1+ of HER2 IHC. HER2-zero includes HER2 0+ which still has some HER2 expression, and shown response to T-DXd in DAISY trial. Further study is needed to determine the lowest cutoff of HER2 for T-DXd.