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Camizestrant Plus CDK 4/6 Inhibitor Improved PFS in Patients With HR+, HER2– Breast Cancer
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Camizestrant is an investigational oral selective estrogen receptor degrader.
Camizestrant (AZD9833; AstraZeneca) plus a CDK 4/6 inhibitor yielded clinically meaningful improvements in progression-free survival (PFS) in first-line treatment of patients with advanced hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2–) breast cancer (BC) with an emergent ESR1 tumor mutation in the phase 3 SERENA-6 trial (NCT04964934).1
Depiction of hormone receptors | Image Credit: © DK_2020 - stock.adobe.com
Breast cancer is among the most frequently diagnosed cancers and a major cause of cancer-related mortality worldwide. In 2022, over 2 million individuals received a breast cancer diagnosis, with global fatalities exceeding 665,000. Approximately 70% of breast tumors fall into the HR+, HER2-category, which is defined by the presence of estrogen and/or progesterone receptors. Estrogen receptors play a key role in driving cancer cell growth.2
For patients with HR+ BC, resistance to CDK4/6 inhibitors and available endocrine therapies presents a significant challenge. Once resistance develops, treatment options become scarce, and survival outcomes decline, with only 35% of patients expected to live beyond 5 years post-diagnosis.2
Camizestrant is an investigational oral selective estrogen receptor degrader (SERD) and complete estrogen receptor antagonist. Preclinical studies have shown that camizestrant exhibits anti-cancer activity, even in models with estrogen receptor-activating mutations. In the phase 2 SERENA-2 trial (NCT04214288), camizestrant improved PFS compared with fulvestrant (Faslodex; AstraZeneca), regardless of ESR1 mutation status or prior CDK4/6 inhibitor treatment in patients with estrogen receptor-positive locally advanced or metastatic BC. In the phase 3 SERENA-6 trial, camizestrant was efficacious with favorable safety when combined with a CDK 4/6 inhibitor such as palbociclib (Ibrance; Pfizer), ribociclib (Kisqali, Novartis Pharmaceuticals Corp.) or abemaciclib (Verzenio; Eli Lilly and Co.).2,3
In the phase 3 trial, 315 adult patients with histologically confirmed HR-positive, HER2-negative advanced BC, undergoing treatment with an aromatase inhibitor in combination with a CDK4/6 inhibitor as first-line treatment, were randomized to receive either camizestrant with a CDK 4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) or treatment with an aromatase inhibitor (anastrozole [Arimidex; AstraZeneca] or letrozole [Femara; Novartis Pharmaceuticals Corporation]) in combination with a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib). The primary end point is PFS, with secondary end points including overall survival (OS) and PFS2, as assessed by an investigator.2
According to data from the planned interim analysis of the trial, treatment with the camizestrant combination yielded significant improvements in PFS. Although immature, PFS2 and OS results demonstrated a positive trend when pairing camizestrant with a CDK 4/6 inhibitor.2
Camizestrant's safety profile when combined with palbociclib, ribociclib, or abemaciclib was in line with each medication's established safety profile. There were extremely few and comparable discontinuations in both arms, and no new safety issues were found.2
“Patients have an urgent need for new treatments that delay disease progression on 1st-line endocrine-based therapies,” François-Clément Bidard, MD, PhD, Professor of Medical Oncology at Institut Curie & UVSQ/Université Paris-Saclay, France, and co-principal investigator for the trial, said in a press release. “The results from SERENA-6 show that switching from an aromatase inhibitor to camizestrant in combination with any of the three CDK4/6 inhibitors after emergence of an ESR1 mutation delays progression of disease and extends the benefit of 1st-line treatment, representing an important step forward for patients and a potential shift in clinical practice.”2
