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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.

Source:

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