Trastuzumab Deruxtecan Is Approved for Patients With Metastatic HER2-Low Breast Cancer

Oncology Nursing NewsOctober 2022
Volume 16
Issue 5

The FDA has approved the first targeted therapy for patients with HER2-low metastatic breast cancer.

The FDA has approved fam-trastuzumab-deruxtecan-nxki (Enhertu) for patients with unresectable or metastatic HER2-low breast cancer. This is the first approved targeted treatment for patients with this disease subtype.1

Findings from the DESTINY-Breast04 trial (NCT03734029) helped to inform the regulatory decision. Investigators of the randomized, multicenter, open label clinical trial randomly assigned 557 adult patients with unresectable or metastatic HER2-low breast cancer to receive either intravenous infusions of trastuzumab deruxtecan at 5.4 mg/kg every 3 weeks or physician’s choice of chemotherapy. The chemotherapy options included capecitabine (Xeloda), eribulin, gemcitabine, paclitaxel, or nab-paclitaxel (Abraxane).1,2 All enrolled patients had already received at last 1 prior line of therapy in the metastatic setting.1,2

The primary end point was progression-free survival (PFS) in patients with hormone receptor–positive disease. Patients who received the antibody-drug conjugate (ADC) achieved a median PFS of 10.1 months (95% CI, 9.5-11.5) vs 5.4 months (95% CI, 4.4-7.1) in the chemotherapy arm (HR, 0.51; 95% CI, 0.40-0.64; P < .0001). Between the 2 arms, the median overall survival (OS) was 23.9 months (95% CI, 20.8-24.8) vs 17.5 months (95% CI, 15.2-22.4), respectively (HR, 0.64; 95% CI, 0.48-0.86; P = .003).3,4

Moreover, investigators observed a 50% reduction in risk of disease progression or death with the experimental agent among randomized population (HR, 0.50; 95% CI, 0.40-0.63). The median PFS among these patients was 9.9 months (95% CI, 9.0-11.3) vs 5.1 months (95% CI, 4.2-6.8) with chemotherapy, and the median OS was 23.4 months (95% CI, 20.0-24.8) vs 16.8 months (95% CI, 14.5-20.0), respectively (HR, 0.64; 95% CI, 0.49-0.84; P = .001).3,4

“Overall survival, which was a secondary end point, went from about 18 months to 24 months, which is really, really impressive,” Sarah Donahue, MPH, NP, AOCNP, a nurse practitioner with Helen Diller Family Comprehensive Cancer Center, said in a conversation about the trial findings with Oncology Nursing News®. “This will be another therapy for patients that they can benefit greatly from.”

According to the FDA, of the 287,850 new cases of female breast cancer expected to be diagnosed in 2022, approximately 80%-85% will be considered a subtype of HER2-negative.1 Among patients who fit that category, 60% are expected to classify as HER2-low and will be able to receive this new targeted therapy, whereas previously only endocrine therapy or chemotherapy options were available.

The recommended dosage of trastuzumab deruxtecan is 5.4 mg/kg given as an intravenous infusion in a 21-day cycle (once every 3 weeks). The first infusion should be administered over 90 minutes. If well tolerated, subsequent infusions may be over a 30-minute period.3

If a modification is necessary the first recommended dose reduction is 4.4 mg/kg, followed by 3.2 mg/kg. Dose reductions should adhere to the 3-week interval, and re-escalation should not be attempted.

The most common adverse events associated with agent use include nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, neutropenia, diarrhea, leukopenia, cough, and thrombocytopenia.

There have been cases of interstitial lung disease (ILD) in patients receiving the ADC. Providers should monitor for and promptly investigate any sigh of cough, dyspnea, fever, or any new respiratory symptoms. Patients should be taught to immediately report any respiratory issues while taking the medicine. If patients experience grade 2 or higher ILD or pneumonitis, trastuzumab deruxtecan must be permanently discontinued.


  1. FDA approves first targeted therapy for HER2-low breast cancer. News release. FDA. August 5, 2022. Accessed August 5, 2022.
  2. Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): results of DESTINY-Breast04, a randomized, phase 3 study. J Clin Oncol. 2022;40 (suppl 17):LBA3. doi:10.1200/JCO.2022.40.17_suppl.LBA3
  3. Enhertu. Prescribing information. Daiichi Sankyo; 2022. Accessed August 5, 2022.
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