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Trastuzumab Deruxtecan vs. Trastuzumab Emtansine in HER2-Positive Metastatic Breast Cancer

In the DESTINY-Breast03 trial, previously treated patients with HER2-positive metastatic breast cancer who received trastuzumab deruxtecan had a significant improvement in overall survival compared with trastuzumab emtansine and the longest reported median progression-free survival for this condition. The investigators concluded that these findings reaffirm “trastuzumab deruxtecan as the standard of care in the second-line setting.”

Conducted at 169 study centers in North America, Asia, Europe, Australia, and South America, the open-label, randomized, multicenter, phase 3 trial included patients aged 18 or older who had HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab and a taxane, an Eastern Cooperative Oncology Group performance status 0–1, and at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumours version 1.1. Randomization of participants to intravenous trastuzumab deruxtecan 5.4 mg/kg or trastuzumab emtansine 3.6 mg/kg every 3 weeks produced these changes in a primary endpoint of progression-free survival: “Median duration of study follow-up was 28.4 months (IQR 22.1–32.9) with trastuzumab deruxtecan and 26.5 months (14.5–31.3) with trastuzumab emtansine. Median progression-free survival by blinded independent central review was 28.8 months (95% CI 22.4–37.9) with trastuzumab deruxtecan and 6.8 months (5.6–8.2) with trastuzumab emtansine (hazard ratio [HR] 0.33 [95% CI 0.26–0.43]; nominal P <0.0001). Median overall survival was not reached (95% CI 40.5 months–not estimable), with 72 (28%) overall survival events, in the trastuzumab deruxtecan group and was not reached (34.0 months–not estimable), with 97 (37%) overall survival events, in the trastuzumab emtansine group (HR 0.64; 95% CI 0.47–0.87]; P = 0.0037). The number of grade 3 or worse treatment-emergent adverse events was similar in patients who received trastuzumab deruxtecan versus trastuzumab emtansine (145 [56%] patients versus 135 [52%] patients). Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 39 (15%) patients treated with trastuzumab deruxtecan and eight (3%) patients treated with trastuzumab emtansine, with no grade 4 or 5 events in either group.”

Source: Lancet