The most common and deadliest malignancy among women is breast cancer (BC), with 2.3 million women diagnosed and 670,000 deaths from the disease globally in 2022. Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20% of BC cases. A third of all these patients will eventually develop brain metastases. With brain metastasis (BM), the prognosis of BC drops significantly, with a median survival of two years, underscoring the need for agents that can penetrate the blood-brain barrier to treat recurrent BCBM.
Trastuzumab, a monoclonal antibody targeting HER2 receptors, has previously been shown to improve overall survival (OS) as a maintenance therapy for patients with BCBM by 13.7 months compared to patients who didn’t receive the treatment in the phase III registHER trial. The inception of antibody drug conjugates (ADCs) has spurred on a host of trastuzumab-linked products which provide improved efficacy and clinical outcomes.
At the European Society of Medical Oncology (ESMO) Congress 2024, recent results from the single-arm open-label DESTINYBreast-012 trial evaluating Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) in patients with metastatic BC were presented. The data demonstrated that the BCBM cohort (n=263) had a 12-month median progression-free survival (PFS) of 61.6%, with an overall response rate (ORR) of 79% for central nervous system metastases. Furthermore, 12-month OS was maintained with Enhertu in 90.3% of patients with active BCBM. Competing against Roche’s Kadcyla (trastuzumab emtansine), Enhertu has demonstrated clinical performance in the DESTINYBreast-03 trial which evaluated patients eligible for second-line treatment of metastatic BC. The trial showed that Enhertu had over double the ORR of Kadcyla and a superior 12-month survival rate without disease progression (75.8% vs 34.1%).
Pipeline ADCs such as BioNTech’s BNT323 could threaten Enhertu’s long-term market position if they demonstrate safety improvement without reduced efficacy. Outside the ADC class, Pfizer’s Tukysa (tucatinib) has been a highly successful HER2-targeting TKI. Tukysa, when combined with trastuzumab and capecitabine doubled median CNS-PFS compared to receiving trastuzumab and capecitabine alone.
GlobalData’s analyst consensus forecast predicts Enhertu will retain its dominant market position in the ADC treatment landscape and reach global sales of $11.2bn by 2030. Kadcyla is projected to achieve $838m by 2030 globally, owing to its less competitive clinical data and introduction of biosimilars eroding its market share. Tukysa emerges as the competitor with the most promise, with an analyst consensus forecast of $1.2bn globally by 2030.
