Trastuzumab deruxtecan decreases risk of disease progression and death in HER2 positive breast cancer: NEJM

USA: A new study published in The New England Journal of Medicine shows that patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who had previously been treated with trastuzumab plus a taxane had a decreased risk of disease progression or death when given trastuzumab deruxtecan than when given trastuzumab emtansine.

Trastuzumab emtansine is the current standard of care for patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer whose illness has progressed after therapy with an anti-HER2 antibody plus a taxane.

Javier Cortés and THE team conducted this study with the objective to compare the disease progression when treated with trastuzumab deruxtecan and trastuzumab emtansine.

This phase 3 open-label, multicenter, randomized study compared the effectiveness and safety of trastuzumab deruxtecan (a HER2 antibody-drug conjugate) to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who had previously been treated with trastuzumab plus a taxane. The primary outcome was progression-free survival (as judged by a blinded independent central review); secondary outcomes were overall objective response, survival, and safety.

The key findings of this study were as follow:

1. At 12 months, 75.8% of 524 randomly assigned patients were alive without disease progression with trastuzumab deruxtecan and 34.1% with trastuzumab emtansine.

2. Trastuzumab deruxtecan had a 94.1% survival rate at 12 months, whereas trastuzumab emtansine had an 85.9% survival rate.

3. Trastuzumab deruxtecan produced an overall response in 79.7% of patients and 34.2% of those who got trastuzumab emtansine.

4. The incidence of drug-related adverse events of any grade was 98.1% with trastuzumab deruxtecan and 86.6% with trastuzumab emtansine, respectively, and 45.1% and 39.8% with trastuzumab emtansine.

5. Adjudicated drug-related pneumonitis occurred or interstitial lung disease in 10.5% of trastuzumab deruxtecan patients and 1.9% of trastuzumab emtansine patients; none of these events were grade 4 or 5.

In conclusion, the findings of this study shows the overall efficiency of trastuzumab deruxtecan rather than trastuzumab emtansine with respect to death or risk of disease progression. Also, Trastuzumab deruxtecan treatment was linked to interstitial lung disease and pneumonitis.

Reference:

Cortés, J., Kim, S.-B., Chung, W.-P., Im, S.-A., Park, Y. H., Hegg, R., Kim, M. H., Tseng, L.-M., Petry, V., Chung, C.-F., Iwata, H., Hamilton, E., Curigliano, G., Xu, B., Huang, (2022). Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. In New England Journal of Medicine (Vol. 386, Issue 12, pp. 1143–1154). Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2115022

Keywords: metastasis, breast cancer, pneumonitis, lung disease, Emtansine, systemic therapy, trastuzumab, malignancy, deruxtecan, oncology, Cancer, HER2, EGFR, NEJM