Moving T-DXd Into Earlier HER2-Positive Breast Cancer Care

At the American Society of Clinical Oncology (ASCO) annual meeting, results from the DESTINY-Breast11 trial showed higher pathologic complete response (pCR) rates with a trastuzumab deruxtecan (T-DXd; Enhertu)-based neoadjuvant regimen compared with standard anthracycline-containing therapy in patients with high-risk HER2-positive early breast cancer.

In this exclusive MedPage Today video, Jame Abraham, MD, of the Cleveland Clinic, reviews the trial’s key efficacy findings, discusses how the results may influence treatment decisions for high-risk patients, and explains why longer-term survival outcomes remain an important unanswered question.

Following is a transcript of his remarks:

DESTINY-11, that’s the phase III trial that looked at a T-DXd-based regimen in the neoadjuvant setting, so that’s in high-risk patients, cT3cN0 or patients with cT0-4cN1-3. So it means locally advanced high-risk patients that are HER2-positive.

So that trial had four arms: T-DXd followed by THP [paclitaxel, trastuzumab (Herceptin), and pertuzumab (Perjeta)]. And then the second arm was dose-dense AC (doxorubicin and cyclophosphamide) followed by THP, and that’s the control arm. And then there was a T-DXd-alone arm. So that arm was closed early by the IDMC [independent data monitoring committee].

So about 927 patients were randomized. The pCR rate, pathological complete rate, in T-DXd alone was 43%. T-DXd followed by THP … was 67.3%, so that’s a pretty high pathologically complete response. And [dose-dense] AC-THP was about 56.3%. So the absolute difference was about 11%. So a huge improvement in pathologically complete response when T-DXd followed by THP was used in high-risk HER2-positive patients. And the benefit was seen in both an HR-positive group, about 61.4% versus 52.3%, and an HR-negative group, 83.1% versus 67.1%.

So it’s really an effective regimen. So how is it going to affect us and how do we use this in clinic? Now we have FDA approval and indications and the guidelines. So in high-risk HER2-positive patients, I think it’s very reasonable to consider T-DXd followed by THP based upon the data, knowing the potential side effects and then knowing that we don’t have survival data, but pCR has been a predictor of survival. And so hopefully we will see a similar translation of survival benefit based upon pCR in this trial.