The human epidermal growth factor receptor type 2 (HER2)-positive breast cancer market across the eight major countries of the US, France, Germany, Italy, Spain, the UK, Japan and China is set to rise from $6.4 billion in 2015 to $9.89 billion in 2025, representing a compound annual growth rate of 4.4%, according to research and consulting firm GlobalData. The company’s latest report states that the adjuvant and neoadjuvant settings remain the greatest contributors to sales, with combined forecasts expected to reach $4.96 billion in 2025, representing 50% of the total HER2-positive market. This surge in market size will be driven primarily by the anticipated launch of Perjeta in the adjuvant setting, which will increase treatment duration compared to the neoadjuvant setting and protect Herceptin sales from biosimilar erosion in established markets. Max Bourgognon, PhD, PharmD, Healthcare Analyst for GlobalData, explains: “The dynamism of the adjuvant and neoadjuvant markets has prompted many companies to position their products in these settings. However, many agents have failed to demonstrate clinical benefit over the currently cemented standard of care, meaning the adjuvant and neoadjuvant settings will remain an exclusive market for anti-HER2 monoclonal antibodies (mAbs), hence constituting the most lucrative opportunity for biosimilar developments.” A new setting in HER2-positive breast cancer will be created upon the launch of Puma Biotechnology’s neratinib. GlobalData expects the drug will gain initial approval by the end of 2017 in the extended adjuvant setting, a space that is currently not utilised in the treatment of HER2-positive breast cancer, which could lead to future growth as additional companies seek to colonize this immature setting. The analyst continues: “Although the efficacy of HER2-targeted therapies substantially improves the life expectancy of patients with HER2-positive disease, it is by nature one of the most aggressive forms of breast cancer, with a poorer prognosis and worse outcomes than for patients with HER2-negative (and HR-positive) disease.” “HER2-targeting mAbs, for example, have failed to deliver benefits to patients with brain metastases, because they cannot pass the blood-brain barrier.” “There are numerous pipeline agents that look to target this underserved patient population, notably the tyrosine kinase inhibitors (TKIs) neratinib and tucatinib, as well as the HER2-targeting mAb margetuximab. However, resistance to kinase inhibitors is common, so innovative therapies to treat TKI-resistant HER2-positive disease will also be required.”