Dr Tarantino on Updated Survival Data With T-DXd in HER2+ Breast Cancer

Paolo Tarantino, MD, researcher, the European Institute of Oncology, clinical research fellow, Dana-Farber Cancer Institute, discusses updated data from the phase 3 DESTINY-Breast03 trial (NCT03529110) investigating fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in patients with metastatic HER2-positive breast cancer.

This pivotal trial was the first head-to-head comparison of T-DXd with the prior standard of care (SOC), ado-trastuzumab emtansine (Kadcyla; T-DM1), in the second line for this patient population, Tarantino begins. Previously reported data from DESTINY-Breast03 showed significant progression-free survival (PFS) and overall survival (OS) benefits with T-DXd vs T-DM1, establishing T-DXd as the preferred second-line treatment option for patients with metastatic HER2-positive breast cancer, he states. However, the exact magnitude of improvement in OS with T-DXd had not been reported in earlier presentations, Tarantino says.

At the 2024 ASCO Annual Meeting, updated findings from an exploratory analysis of the study were presented and simultaneously published in Nature Medicine, Tarantino reports. Results showed that T-DXd (n = 261) produced a median investigator-assessed OS of 52.6 months (95% CI, 48.7-not evaluable [NE]). T-DXd prolonged the median OS by 9.9 months compared with T-DM1 (n = 263), which produced a median OS of 42.7 months (95% CI, 35.4-NE; HR, 0.73 [95% CI, 0.56-0.94]). The 36- and 42-month OS rates with T-DXd were 67.6% (95% CI, 61.3%-73.0%) and 62.5% (95% CI, 56.2%-68.3%), respectively; these respective rates with T-DM1 were 55.7% (95% CI, 49.2%-61.7%) and 50.1% (95% CI, 43.6%-56.2%).

Additionally, the updated data demonstrated that T-DXd was associated with a median PFS of 29.0 months (95% CI, 23.7-40.0) vs 7.2 months (95% CI, 6.8-8.3) with T-DM1 (HR, 0.30; 95% CI, 0.24-0.38). The 36-month PFS rates with T-DXd and T-DM1 were 45.7% (95% CI, 38.9%-52.2%) and 12.4% (95% CI, 8.1%-17.7%), respectively. These findings reinforce the already-established superiority of T-DXd over T-DM1 in terms of both PFS and OS, further solidifying T-DXd’s position as the SOC for patients who have progressed on chemotherapy and trastuzumab (Herceptin) in earlier lines, Tarantino explains. Anticipated results from the ongoing phase 3 DESTINY-Breast09 trial (NCT04784715) will further elucidate a potential role for T-DXd with or without pertuzumab (Perjeta) in the first-line setting, Tarantino concludes