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Camizestrant with a CDK 4/6 inhibitor had a statistically significant and clinically meaningful improvement in PFS in HR+/HER2– advanced breast cancer.
Among patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer whose tumors have an emergent ESR1 mutations, first-line treatment with camizestrant in combination with a CDK 4/6 inhibitor demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS).
According to a press release from AstraZeneca, PFS serves as the primary end point of the phase 3 SERENA-6 clinical trial which evaluated the camizestrant combination versus standard-of-care treatment with an aromatase inhibitor (AI) in combination with a CDK4/6 inhibitor; the release shared positive high-level results from a planned interim analysis of the trial. Moreover, key secondary end points of time to second disease progression and overall survival were immature at the time of this interim analysis; however, the trial will continue as planned to further assess these end points.
Progression-free survival (PFS): the amount of time a patient lives without their disease progressing.
Second disease progression: how long it takes for a patient's disease to progress again after starting second-line therapy.
Overall survival: the amount of time a person lives after being diagnosed with a disease or starting treatment.
“Patients have an urgent need for new treatments that delay disease progression on 1st-line endocrine-based therapies,” Dr. François-Clément Bidard, professor of Medical Oncology at Institut Curie & UVSQ/Université Paris-Saclay, in France, and co-principal investigator for the trial. “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 first-line treatment, representing an important step forward for patients, and a potential shift in clinical practice.”
Regarding safety, the combination of camizestrant plus a CDK 4/6 inhibitor in SERENA-6 was consistent with the known safety profile of each medicine. Importantly, treatment discontinuations were low and similar in both treatment arms, and no new safety concerns were identified.
The press release stated that additional data will be shared at an upcoming medical meeting and with global regulatory authorities, respectively.
Globally, approximately 200,000 patients with HR-positive breast cancer receive first-line treatment, typically with endocrine therapies, often combined with CDK4/6 inhibitors; however, many patients with advanced disease develop resistance to these therapies. Mutations in the ESR1 gene are a major driver of endocrine resistance and are associated with poor outcomes, which develop in approximately 30% of patients with endocrine-sensitive HR-positive disease during first-line therapy, even without disease progression.
Once resistance to CDK4/6 inhibitors and endocrine therapies occurs, treatment options are limited for patients with breast cancer, and survival rates decline, with only 35% of patients expected to live beyond five years. Research efforts focus on optimizing endocrine therapy, overcoming resistance and identifying new treatments, which led to the initiation of the SERENA-6 clinical trial.
The double-blind, randomized trial is evaluating the efficacy and safety of camizestrant in combination with a CDK4/6 inhibitor — either Ibrance (palbociclib), Kisqali (ribociclib) or Verzenio (abemaciclib) — versus treatment with an AI — either Arimidex (anastrozole) or Femara (letrozole) — in combination with one of the three CDK4/6 inhibitors in patients with HR-positive, HER2-negative advanced breast cancer; this includes patients with either locally advanced disease or metastatic disease whose tumors have an emergent ESR1 mutation. Enrolling 315 eligible adult patients with histologically confirmed disease, patients underwent treatment with an AI in combination with a CDK4/6 inhibitor as first-line therapy.
Camizestrant is a potent, next-generation oral selective estrogen receptor degrader and complete estrogen receptor antagonist. The agent is currently being investigated in phase 3 trials for the treatment of patients with HR-positive breast cancer, including SERENA-6, SERENA-4, CAMBRIA-1 and CAMBRIA-2 trials, which is aiming to better understand the safety and efficacy of the agent.
"These impressive results demonstrate the versatility of camizestrant in combination with all the widely approved CDK4/6 inhibitors to provide a well-tolerated new potential treatment option in the first-line setting for the one in three patients with HR-positive, HER2-negative advanced breast cancer whose tumors develop ESR1 mutations during treatment with an aromatase inhibitor in combination with a CDK4/6 inhibitor. This critical read-out moves us one step closer to realizing the potential of camizestrant to become a new standard-of-care as we look to shift the treatment paradigm and establish this new endocrine therapy backbone in HR-positive breast cancer,” Susan Galbraith, executive vice president, Oncology Hematology R&D, AstraZeneca, concluded in the news release.
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