Trastuzumab Deruxtecan Yields Clinically Meaningful Outcomes in HER2-Low Metastatic Breast Cancer


Patients with HER2-low metastatic breast cancer achieved clinically meaningful improvement in progression-free survival following treatment with fam-trastuzumab deruxtecan-nxki.

Treatment with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) yielded clinically meaningful improvements in key outcome measures for patients with HER2-low unresectable or metastatic breast cancer compared with investigator’s choice of chemotherapy, according to findings from the phase 3 DESTINY-Breast04 Trial (NCT03734029).1

Patients experienced a statistically significant and clinically meaningful progression-free survival (PFS) and overall survival (OS) benefit following treatment with T-DXd regardless of hormone receptor (HR) status.

“[T-DXd] continues to redefine the treatment of HER2 targetable cancers. DESTINY-Breast04 is the first ever phase 3 trial of a HER2 directed therapy in patients with HER2 low metastatic breast cancer to show a statistically significant and clinically meaningful benefit in [PFS] and overall survival compared to standard treatment,” Ken Takeshita, MD, global head of R&Dat Daiichi Sankyo, said in a press release. “We look forward to sharing the detailed findings of DESTINY-Breast04 with the medical community and initiating discussions with regulatory agencies globally with the goal of potentially bringing [T-DXd] to patients with metastatic breast cancer previously considered to be HER2 negative.”

Patients who were included in the trial had centrally confirmed HER2 status, which was defined as an immunohistochemistry score of 1+ or 2+ with negative in-situ hybridization score. The study met its primary end point of superior PFS in those with pretreated HR-positive, HER2-low disease over chemotherapy in addition to meeting key secondary end points of OS in patients with both HR-positive disease and in those regardless of HR status.

In terms of safety, T-DXd had a safety profile that was consistent with prior clinical findings; no new safety signals were observed. Investigators reported that the incidence of interstitial lung disease (ILD) was consistent with that of later-line HER2 positive breast cancer trials, with a lower rate of grade 5 ILD identified by independent adjudication committee.

“Today’s historic news from DESTINY-Breast04 could reshape how breast cancer is classified and treated,” Susan Galbraith, MBBChir, PhD, executive vice president of Oncology R&D at AstraZeneca, concluded. “A HER2 directed therapy has never before shown a benefit in patients with HER2 low metastatic breast cancer. These results for [T-DXd] are a huge step forward and could potentially expand our ability to target the full spectrum of HER2 expression, validating the need to change the way we categorize and treat breast cancer.”

Data on the study will be presented at an upcoming medical meeting.

T-DXd was previously granted priority review by the FDA in January 2022 for patients with HER2-positive unresectable/metastatic breast cancer who previously received treatment with a previous anti-HER2 regimen based in data from the DESTINY-Breast03 (NCT03529110).2


  1. ENHERTU® significantly improved both progression-free and overall survival in DESTINY-Breast04 trial in patients with HER2 low metastatic breast cancer. News release. Daiichi Sankyo. February 21, 2022. Accessed February 21, 2022.
  2. CORRECTING and REPLACING ENHERTU® granted priority review in the US for patients with HER2-positive metastatic breast cancer treated with a prior anti-HER2-based regimen. News release. AstraZeneca and Daiichi Sankyo. January 17, 2022. Accessed February 21, 2022.
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