Dr Fenton on Findings from the DESTINY-Breast02 Trial in HER2+ Breast Cancer

Mary Anne Fenton, MD, clinical director, Breast Medical Oncology, Rhode Island Hospital, director, Quality, Lifespan Cancer Institute, associate clinical professor, medicine, Warren Alpert Medical School, Brown University, discusses findings from the phase 3 DESTINY-Breast02 trial (NCT03523585) in patients with HER2-positive metastatic breast cancer.

The trial evaluated fam-trastuzumab deruxtecan-nxki (Enhertu) vs treatment of physician's choice in patients with HER2-positive unresectable and/or metastatic breast cancer who received prior treatment with ado-trastuzumab emtansine (T-DM1; Kadcyla). Key eligibility criteria for the study included centrally confirmed HER2-positive disease by immunohistochemistry or in situ hybridization. Physician’s choice of treatment included a combination of capecitabine with either trastuzumab (Herceptin) or lapatinib (Tykerb).

Findings from the primary analysis of the randomized, open-label, multicenter trial presented at the 2022 San Antonio Breast Cancer Symposium showed that the median progression-free survival (PFS) for patients who received trastuzumab deruxtecan (n = 406) was 17.8 months (95% CI, 14.3-20.8) vs 6.9 months (95% CI, 5.5-8.4) for those given physician’s choice of treatment (n = 202), translating to a 64% reduction in the risk of disease progression or death (HR, 0.3589; 95% CI, 0.2840-0.4535; P < .0000001).

The PFS benefit was observed across all patient subgroups, Fenton says, including patients older or younger than 65 years of age, patients with hormone receptor–positive or ­–negative disease, prior treatment with pertuzumab (Perjeta), visceral disease, and baseline treated brain metastases. There was an early separation in the Kaplan-Meier curves for PFS, indicating that trastuzumab deruxtecan overcame early drug resistance. Additionally, investigators observed a significant change in tumor size. Although no new safety signals were reported with a longer follow-up, early recognition and management of pneumonitis remains important for patients treated with trastuzumab deruxtecan, Fenton concludes.