Trial in Progress: Real-World Experience of Trastuzumab Deruxtecan in HER2+ and HER2-low Unresectable and/or MBC (DESTINY-Breast-RESPOND Trial)

Based on positive results from the DESTINY-Breast03 and DESTINY-Breast04 clinical trials, the HER2-directed antibody–drug conjugate trastuzumab deruxtecan (T-DXd) was approved for the treatment of patients with unresectable or metastatic HER2+ breast cancer who have received a prior anti–HER2-based regimen, or patients with unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. The DESTINY-Breast-RESPOND (NCT05592483) trial was initiated to evaluate real-world clinical use, effectiveness, tolerability, and patient experience of T-DXd in patients with HER2+ or HER2-low unresectable and/or metastatic breast cancer (MBC) in a real-world setting.

The DESTINY-Breast-RESPOND trial is a multicenter, multi-country, prospective, observational study that will enroll2 patient cohorts, HER2+ and HER2-low unresectable and/or MBC. The HER2+ cohort will recruit patients in several regions globally, whereas the HER2-low cohort will recruit patients in North America only.

Inclusion criteria include prior treatment with a trastuzumab-containing regimen in the metastatic setting or evidence of disease progression within 6 months of neoadjuvant or adjuvant treatment (HER2+ cohort), or prior chemotherapy in the metastatic setting or evidence of disease progression within 6 months of adjuvant chemotherapy (HER2-low cohort). Patient-reported outcome questionnaires on tolerability and safety will be administered, in addition to maintaining a daily patient nausea/vomiting symptom diary.

The primary end point is real-world time to next treatment from T-DXd initiation (both cohorts) and treatment patterns (HER2+ cohort only); secondary end points include treatment patterns (HER2-low cohort), physician-reported safety events of interest (SEI; including nausea/vomiting, fatigue, alopecia, interstitial lung disease [ILD/pneumonitis, LVEF decrease) and evaluation of prophylactic and reactive treatments for SEI management, real-world time to T-DXd discontinuation, and patient-reported tolerability. Patients will be observed until end of study (approximately 60% of patients receive subsequent treatment or have died), withdrawal from study, or loss to follow-up, whichever occurs first. Study end points will be analyzed separately for HER2+ and HER2-low cohorts.

Enrollment is planned across 120 sites, with 29 currently active sites.

Source:

O’Shaughnessy J, Basho R, Lustberg M, et al. A multicenter, prospective, observational study of patients receiving trastuzumab deruxtecan for the treatment of HER2-positive and HER2-low unresectable and/or metastatic breast cancer: DESTINY-Breast-RESPOND. Presented at the 46th San Antonio Breast Cancer Symposium Annual Meeting, December 5-9, 2023; San Antonio, TX: Abstract PO4-17-02.