Dr McCann on the Expanding Role of T-DXd in HER2+ Breast Cancer Management

“I think [the DESTINY-Breast05 regimen] is going to be implemented quickly. It’ll be interesting to see what the uptake rate is going to be with the neoadjuvant strategy [from] DESTINY-Breast11 vs this strategy. I think this one is a winner.”

Kelly Elizabeth McCann, MD, PhD, an associate professor at the University of California San Diego, discussed the clinical implications of the FDA approval of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for the treatment of adult patients with HER2-positive (immunohistochemistry [IHC] 3+ or in situ hybridization [ISH] positive) breast cancer who have residual invasive disease following neoadjuvant HER2-targeted therapy.

This regulatory decision was supported by findings from the phase 3 DESTINY-Breast05 trial (NCT04622319), in which patients who received T-DXd (n = 818) achieved a 3-year invasive disease-free survival rate of 92.4% (95% CI, 89.7%-94.4%) compared with 83.7% (95% CI, 80.2%-86.7%) among those who received ado-trastuzumab emtansine (Kadcyla; T-DM1; n = 817; HR, 0.47; 95% CI, 0.34-0.66; P < .0001).

McCann explained that the DESTINY-Breast05 trial design is similar to that of the phase 3 KATHERINE trial (NCT01772472), which showed that T-DM1 reduced the risk of invasive breast cancer or death compared with trastuzumab (Herceptin) alone in patients with HER2-positive early breast cancer with residual invasive disease after completing neoadjuvant therapy. She also contextualized the DESTINY-Breast05 findings within the scope of the phase 3 DESTINY-Breast11 trial (NCT05113251), which demonstrated a pathologic complete response rate of 67.3% (95% CI, 61.9%-72.4%) in patients with HER2-positive (IHC 3+ or ISH+) stage II or III breast cancer, as determined by an FDA-authorized test, who were treated with T-DXd followed by a taxane plus trastuzumab and pertuzumab (Perjeta; THP; n = 321) vs 56.3% (95% CI, 50.6%-61.8%) in patients treated with doxorubicin and cyclophosphamide followed by THP (n = 320; P = .003). In the announcement of the FDA approval of post-neoadjuvant T-DXd, the FDA simultaneously announced the approval of T-DXd followed by THP for the DESTINY-Breast11 indication.

Ultimately, McCann predicted that post-neoadjuvant T-DXd will be quickly adopted as a treatment strategy in HER2-positive breast cancer clinical practice, although uptake rates may be affected by the availability of T-DXd followed by THP in the early-stage setting.