Dr Fenton on Trastuzumab Deruxtecan Vs Trastuzumab Emtansine 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-Breast03 trial (NCT03529110) in patients with metastatic, HER2-positive breast cancer.

Updated findings from DESTINY-Breast03 were presented by Sara A. Hurvitz, MD, of the University of California, Los Angeles, at the 2022 San Antonio Breast Cancer Symposium. This trial enrolled patients with centrally confirmed, HER2-positive, locally advanced or metastatic breast cancer who had previously received trastuzumab (Herceptin) and a taxane. Accordig to Fenton, this patient population was similar to that of the phase 3 DESTINY-Breast02 trial (NCT03523585), which evaluated the efficacy and safety of fam-trastuzumab deruxtecan-nxki (Enhertu) vs physician’s choice of treatment in patients with HER2-positive metastatic breast cancer previously treated with ado-trastuzumab emtansine (Kadcyla). DESTINY-Breast03 randomized patients to receive either trastuzumab deruxtecan or trastuzumab emtansine in the second-line setting

Trastuzumab emtansine is a HER2-targeted, microtubule-stabilizing antibody-drug conjugate (ADC) with about 3 chemotherapy molecules per antibody, Fenton explains. Trastuzumab deruxtecan, another ADC, has a higher payload than trastuzumab emtansine, as well as a cleavable linker with a bystander effect.

In DESTINY-Breast03, patients who received trastuzumab deruxtecan achieved a longer progression-free survival (PFS) and overall survival (OS) than those who received trastuzumab emtansine. An early separation of the curves was observed between the 2 arms, indicating that trastuzumab deruxtecan can overcome early drug resistance and induce durable responses, Fenton emphasizes. The median PFS was 28.8 months in the trastuzumab deruxtecan arm vs 6.8 months in the trastuzumab emtansine arm. The median OS was not yet reached (NR) with 72 OS events vs NR with 97 OS events in the trastuzumab deruxtecan and trastuzumab emtansine arms, respectively.

Additionally, similarly to the findings from DESTINY-Breast02, trastuzumab deruxtecan provided a consistent survival benefit across all prespecified patient subgroups in DESTINY-Breast03, including patients with hormone receptor (HR)–positive disease, those with HR-negative disease, those with prior pertuzumab (Perjeta) exposure, and those with visceral disease or brain metastases at baseline, Fenton notes.

Furthermore, as in DESTINY-Breast02, the most common treatment-related adverse effects experienced by patients who received trastuzumab deruxtecan in DESTINY-Breast03 included nausea, vomiting, alopecia, constipation, and anemia, Fenton explains. Careful monitoring of patients receiving trastuzumab deruxtecan is crucial, as this agent is associated with high rates of pneumonitis, Fenton says.

Many guidelines now recommend trastuzumab deruxtecan as second-line therapy in patients with HER2-positive locally advanced or metastatic breast cancer, Fenton adds. Ongoing trials are investigating the efficacy of this agent in the frontline setting for patients with newly metastatic HER2-positive breast cancer, Fenton concludes.