AstraZeneca has presented results for the SERENA-6 trial at the American Society for Medical Oncology (ASMO)’s 2025 conference, held in Chicago, Illinois from 30 May to 3 June. The SERENA-6 trial compares camizestrant, an oral selective oestrogen receptor degrader (SERD), in combination with a CDK4/6 (cyclin-dependent kinase) inhibitor, which could be Pfizer’s Ibrance (palbociclib), Eli Lilly’s Verzenio (abemaciclib), or Novartis’ Kisqali (ribociclib), with aromatase inhibitors in combination with a CDK4/6 inhibitor in hormone receptor-positive human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer patients with detectable mutation in the oestrogen receptor alpha (ESR1) gene during first-line treatment.
The trial used a novel design in which patients underwent liquid tumour biopsies throughout their standard first-line treatment during routine scans to detect ESR1 mutation in circulating tumour DNA (ctDNA) before the disease progressed. If ESR1 was detected, patients were randomised to continue aromatase inhibitors plus CDK4/6 or to switch to camizestrant + CDK4/6.
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Camizestrant + CDK4/6 significantly increased progression-free survival (PFS) to 16.0 months from 9.2 months with a hazard ratio (HR) of 0.44 (95% confidence interval [CI]: 0.31–0.60). While subsequent progression, also known as PFS2, data was immature at the time of analysis, it was trending positively with an HR of 0.52. Overall survival was also immature at the time of analysis.
In the camizestrant + CDK4/6 arm, 60% of patients experienced grade 3 or above adverse events, while only 46% of patients on the aromatase inhibitors + CDK4/6 arm did. The rate of therapy discontinuation due to adverse events was low in both arms (1% for camizestrant and 2% for aromatase inhibitors). Camizestrant also delayed the median onset of global health deterioration as reported by patients from 6.4 months (95% CI: 2.8, 14.0) to 23.0 months (95% CI: 13.8, not calculable). This positive trial outcome has resulted in the US Food and Drug Administration (FDA) granting the regimen breakthrough designation.
AstraZeneca may be pleased with the PFS data for camizestrant. However, questions about how burdensome the SERENA-6 regimen will be to cancer clinics and healthcare systems remain, as regular liquid biopsies and ctDNA detection, required to switch patients positive for ESR1 to camizestrant, will be difficult for smaller or rural clinics to accommodate. The cost burdens of CDK4/6 inhibitors are already high, and adding the oral SERD camizestrant instead of the relatively cheap generic endocrine therapies will increase the cost for payers further. The FDA approval of the SERENA-6 regimen based on this positive efficacy data is likely, but its uptake may be slow as healthcare systems and clinics adjust their practices.
The ESR1+ HR+/HER2- metastatic breast cancer space has seen a significant development since the approval of Stemline Menarini’s oral SERD Orserdu (elacestrant) in the second-line setting after progression on CDK4/6 + endocrine therapy in January 2023. Eli Lilly posted positive results in December 2024 for its oral SERD imlunestrant, while Pfizer announced positive results for its ER-targeting PROTAC, vepdegestrant, at ASCO 2025, both in the second-line setting. AstraZeneca has successfully sidestepped the crowded second-line setting with its novel treatment design. However, with Roche’s oral SERD, giredestrant, in a trial in first-line ER+/HER2- metastatic breast cancer in combination with Ibrance, with a readout expected in December 2025, competition may be coming.
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By GlobalDataAccording to GlobalData’s analyst consensus forecast, camizestrant will reach blockbuster status in 2030 with total sales worth $1.1 billion, while vepdegestrant reaches $1.3 billion, giredestrant sells $1.1 billion, imlunestrant receives $329 million, and Orserdu only $174 million. Camizestrant and AstraZeneca still have a lot of competition in this space, but their novel strategy could help them carve a niche.
