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Trastuzumab deruxtecan significantly improved overall survival compared to trastuzumab emtansine in a multi-center phase 3 trial.

Human epidermal growth factor receptor 2 (HEGFR 2) is overexpressed in 15–20% of breast cancers. Currentlu, for HER2-positive metastatic breast cancer, pertuzumab and trastuzumab, plus a taxane, are first-line treatments. Second-line therapy is trastuzumab deruxtecan or trastuzumab emtansine, both of which consist of a humanized anti-HER2 monoclonal antibody linked to a strong cytotoxic payload.

This study, published in The Lancet, examined the relative benefits and risks of trastuzumab deruxtecan and trastuzumab emtansine.

Study Population

The DESTINY-Breast03 study, which was an open-label, multicenter, phase 3 trial, randomly assigned 18-year-old women with HER2-positive breast cancer that was either not resectable or had spread and gotten worse after receiving trastuzumab plus a taxane. The experiment was undertaken at 169 North American, Asian, European, Australian, and South American research centers.

Participants received intravenous trastuzumab deruxtecan (5.4 mg/kg) or emtansine (3.6 mg/kg) every 3 weeks in a 1:1 randomization. Trastuzumab deruxtecan (n = 261) or trastuzumab emtansine (n = 263) were randomly assigned to 524 of the 699 screened patients. The median follow-up length for trastuzumab deruxtecan was 28.4 months, whereas that for trastuzumab emtansine was 26.5 months.

Progression-Free Survival and Median Overall Survival After Treatment

The median progression-free survival was 28.8 months for trastuzumab deruxtecan and 6.8 months for trastuzumab emtansine (p<0.0001). There was no statistically significant difference in overall survival between the trastuzumab deruxtecan and trastuzumab emtansine groups, with 72 (28%) overall survival events in the trastuzumab deruxtecan group and 97 (37%) in the trastuzumab emtansine group.

Adverse Events Reported During the Study

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Trastuzumab deruxtecan and trastuzumab emtansine patients had similar rates of grade 3 or worse treatment-emergent adverse events (145 [56%] and 135 [52%], respectively). Interstitial lung disease or pneumonitis occurred in 39 (15%) trastuzumab deruxtecan patients and 8 (3%) trastuzumab emtansine patients. No grade 4 or 5 events were noted.

The Response Rate of Patients After Treatment

The study showed a 79% objective response rate (205 patients) for trastuzumab deruxtecan and 35% (92 patients) for trastuzumab emtansine. The trastuzumab deruxtecan group had 55 (21%) complete responses and 150 (57%) partial responses, whereas the emtansine group had 25 (10%) full responses and 67 (25%) partial responses. The study also found a median response duration of 36.6 months for trastuzumab deruxtecan and 23.8 months for trastuzumab emtansine.

In participants with HER2-positive metastatic breast cancer, trastuzumab deruxtecan had a longer median progression-free survival and better overall survival than trastuzumab emtansine. This confirms that it should be used as the second-line standard of care. With extended therapy, trastuzumab deruxtecan showed reasonable safety.


Hurvitz, S. A., Hegg, R., Chung, W. K., Im, S., Jacot, W., Ganju, V., Chiu, J. W. Y., Xu, B., Hamilton, E., Madhusudan, S., Iwata, H., Altıntaş, S., Henning, J., Curigliano, G., Pérez-García, J. M., Kim, S., Petry, V., Huang, C., Li, W., . . . Cortés, J. (2023). Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. The Lancet, 401(10371), 105–117. https://doi.org/10.1016/s0140-6736(22)02420-5