Breast cancer remains a significant global health challenge, with 2.3 million new diagnoses and 670,000 deaths reported in 2022. Approximately 20% of breast cancer cases involve overexpression of the human epidermal growth factor receptor 2 (HER2), and about one-third of these patients develop brain metastases (BCBM), which drastically reduces survival rates to a median of two years. This underscores the urgent need for effective therapies that can penetrate the blood-brain barrier.
Enhertu's Impact on Metastatic BCBM
At the European Society of Medical Oncology (ESMO) Congress 2024, results were presented from the DESTINYBreast-012 trial, an open-label study evaluating Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) in metastatic breast cancer patients. The BCBM cohort (n=263) showed a 12-month median progression-free survival (PFS) of 61.6% and an overall response rate (ORR) of 79% for central nervous system metastases. Furthermore, Enhertu maintained a 12-month overall survival (OS) rate of 90.3% in patients with active BCBM.
Comparison with Existing Therapies
Enhertu's performance was compared to Roche's Kadcyla (trastuzumab emtansine) in the DESTINYBreast-03 trial, which focused on patients eligible for second-line treatment of metastatic breast cancer. Enhertu demonstrated more than double the ORR of Kadcyla and a superior 12-month survival rate without disease progression (75.8% vs 34.1%). Trastuzumab, a monoclonal antibody targeting HER2, has previously shown a 13.7-month improvement in overall survival as maintenance therapy for BCBM patients in the registHER trial, compared to those without the treatment.
Competitive Landscape
While Enhertu is poised to dominate the ADC market, other therapies are emerging. BioNTech's BNT323, an ADC in the pipeline, could challenge Enhertu if it demonstrates improved safety without compromising efficacy. Pfizer's Tukysa (tucatinib), a HER2-targeting TKI, has shown promise when combined with trastuzumab and capecitabine, doubling the median CNS-PFS compared to trastuzumab and capecitabine alone.
Market Projections
GlobalData’s analyst consensus forecast predicts Enhertu will achieve global sales of $11.2 billion by 2030, solidifying its dominant position in the ADC treatment landscape. Kadcyla is projected to reach $838 million by 2030, while Tukysa is forecasted to achieve $1.2 billion globally, marking it as a significant competitor.
