The Best Treatment Options for Stage 4 HER2-Positive Breast Cancer

HER2-positive breast cancer means that tumour cells produce too much of a protein called HER2, causing rapid growth. The HER2 protein activates a signalling pathway that helps cells grow and multiply, allowing cancer cells to proliferate rapidly. Many new targeted drugs specifically for HER2-positive breast cancer have now been developed. As the number of options grows, the question is which treatment is most effective for patients.

One notable oncology study of 2022 concerned 2 newer-generation targeted drugs used in HER2-positive breast cancer: trastuzumab deruxtecan (T-DXd, Enhertu) and trastuzumab emtansine (T-DM1, Kadcyla). These drugs were compared head-to-head in DESTINY-Breast03, whose updated results were presented at the 2022 San Antonio Breast Cancer Symposium.

DESTINY-Breast03 enrolled patients with advanced HER2-positive breast cancer previously treated with trastuzumab and taxanes. It compared Kadcyla and Enhertu, newer-generation anti-HER2 treatments. Until this study, the most suitable treatment for patients in this situation remained uncertain.

• In this study of 524 patients, median overall survival with trastuzumab deruxtecan (T-DXd, Enhertu) was significantly better than with trastuzumab emtansine (T-DM1, Kadcyla). T-DXd reduced the risk of death by 36% (hazard ratio 0.64).
• In the T-DXd group, survival rates at year 1 and year 2 were 94.1% and 77.4%, respectively; in the T-DM1 group, the corresponding year 1 and year 2 rates were 86% and 69.9%.
• Median progression-free survival was 4 times longer with T-DXd: 28.8 months versus 6.6 months.
• An objective treatment response occurred in 78.5% of patients receiving T-DXd, while one in every 5 patients (21.1%) had a complete radiological response.
• Rates of severe adverse effects (grade ≥3) with T-DXd and T-DM1 were 56% and 52%, respectively. Interstitial lung disease occurred in 15% and 3%, respectively.

In conclusion, this study indicates that T-DXd is a more effective treatment option than T-DM1 for patients with HER2-positive breast cancer whose cancer has progressed after taxane and trastuzumab treatment.