Dr. Force on the Efficacy of Trastuzumab Deruxtecan in the DESTINY-Breast02 Trial for HER2+ Breast Cancer

Jeremy Force, DO, assistant professor of medicine, in the Department of Medical Oncology, Duke Health, a member of the Duke Cancer Institute, and an oncologist at the Duke Cancer Center Breast Clinic, discusses the efficacy of fam-trastuzumab deruxtecan-nxki (Enhertu) in pretreated patients with HER2-positive breast cancer on the phase 3 DESTINY-Breast02 trial (NCT03523585).

The study investigated the use of the antibody-drug conjugate (ADC) trastuzumab deruxtecan compared with investigator's choice of treatment in patients with unresectable, metastatic HER2-positive breast cancer that has been previously treated with ado-trastuzumab emtansine (Kadcyla). Physician’s choice of treatment included trastuzumab (Herceptin) plus capecitabine or lapatinib (Tykerb) plus capecitabine.

Findings from DESTINY-Breast02 presented at the 2022 San Antonio Breast Cancer Symposium showed that trastuzumab deruxtecan led to a clinically meaningful improvement in the progression-free survival (PFS) and overall survival (OS) compared with physician’s choice of treatment. Patients treated with trastuzumab deruxtecan experienced a median PFS of 17.8 months compared with 6.9 months for those in the control arm. The median OS was 39.2 months and 26.5 months in the trastuzumab deruxtecan and the control arm, respectively.

Additionally, patients in the trastuzumab deruxtecan arm experienced an improvement in overall response rate at 69.7%, compared with 29.2% for the physician’s choice of treatment arm.

Data surrounding trastuzumab deruxtecan from DESTINY-Breast02 and other clinical trials have continued to show the positive benefit of the ADC for patients with HER2-positive breast cancer, Force says. As trastuzumab deruxtecan moves forward into earlier lines of therapy and potentially into the adjuvant setting, addressing interstitial lung disease associated with the ADC will be important in the adverse effect management of these patients, Force notes.

Along with DESTINY-Breast02, the phase 3 DESTINY-Breast03 (NCT03529110) and DESTINY-Breast04 (NCT03734029) trials have demonstrated the ability of trastuzumab deruxtecan to improve outcomes for patients with HER2-positive and HER2-low breast cancer, Force concludes.