AstraZeneca recently announced positive toplined interim results from SERENA-6, a randomised, multicentre, double-blind Phase III trial. The trial evaluated the effectiveness of AstraZeneca’s camizestrant, an investigational next-generation oral selective estrogen receptor degrader (SERD), in combination with one of three cyclin-dependent kinase (CDK) 4/6 inhibitors – Pfizer’s Ibrance, Eli Lilly’s Verzenio or Novartis’ Kisqali – versus the standard-of-care, an aromatase inhibitor in combination with a CDK4/6 as a front-line therapy for patients ER-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer with detectable estrogen receptor alpha (ESR1) mutation. ESR1 mutation is a key driver of resistance that can develop during or after endocrine treatment, and it is now standard clinical practice to test for ESR1 mutations via liquid biopsy.
ER-positive/HER2-negative breast cancer is the most common subtype of breast cancer that is diagnosed in developed countries, and is often treated with endocrine therapies that target estrogen receptor-driven breast cancer in combination with CDK4/6 inhibitors. According to leading data and analytics company GlobalData’s HER2-Negative Breast Cancer: Epidemiology Forecast to 2028 report, the number of diagnosed incident cases of invasive hormone receptor-(HR) positive/HER2-negative breast cancer in women in the eight major markets (US, France, Germany, Italy, Spain, UK, Japan, and China) will grow from 625,674 in 2025 to 648,377 in 2028.
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The trial results demonstrated the statistically significant and clinically meaningful primary endpoint of progression-free survival (PFS). While secondary endpoints, including progression-free survival 2 (PFS2) and overall survival (OS), were not yet mature, interim data indicated a positive trend in PFS2, and grade 3 or worse treatment-emergent adverse events were low in the Phase II SERENA-2 clinical trial. However, it is too early to draw definitive conclusions, as OS data for patients with ESR1 mutations has not yet been assessed in the interim analysis. Additionally, SERENA-6 does not compare early SERD use to post-progression treatment, leaving a critical gap in understanding its long-term benefit. In 2023, the US Food and Drug Administration approved the first SERD, Stemline Therapeutics’ Orserdu, for the treatment of patients with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer after progression on prior endocrine therapy. Despite SERENA-6 only introducing camizestrant after the detection of ESR1 mutation, AstraZeneca is positioning it as a first-line therapy, aiming to establish its use earlier in treatment. This strategic move could help AstraZeneca gain a first-mover advantage before the SERENA-4 first-line trial reads out in August 2026. The company is further strengthening its presence with five Phase III trials for camizestrant in breast cancer. AstraZeneca will face direct competition in the HR-positive, HER2-negative breast cancer market, particularly from Roche’s giredestrant, which is undergoing five Phase III trials (persevERA). Additionally, Arvinas/Pfizer’s vepdegestrant is another SERD being investigated in Phase III (VERITAC-3), with an expected completion date of August 2028. Eli Lilly’s imlunestrant showed positive results for patients with HR-positive/HER2-negative breast cancer with ESR1 mutation status.
According to GlobalData’s analyst consensus forecast, global sales of camizestrant are expected to reach $982m by 2030. Comparatively, giredestrant is expected to generate sales of $1.10bn, vepdegestrant is expected to generate sales of $1.13bn, and imlunestrant is expected to generate sales of $165m. With increasing competition in the oral SERD space, AstraZeneca’s success with camizestrant will depend on its ability to establish a clear first-line role ahead of key rivals such as Roche, Pfizer, and Eli Lilly.
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