Promising Data for Many Women With Advanced Breast Cancer
- While it’s not yet approved, a drug called camizestrant is showing real promise in improving survival for patients with a specific type of advanced breast cancer classified as hormone receptor (HR)-positive, HER2-negative.
- The positive results were illustrated in a trial called SERENA-6 where camizestrant, which belongs to a class of drugs called selective estrogen receptor degraders (SERDs), was added to treatment plans.
- The drug targets ESR1 mutations, which often develop in this subset of patients and can lead to treatment resistance. About 30% of patients with endocrine sensitive, HR-positive disease will develop this mutation during initial treatment
- The data from SERENA- 6 will be presented at an upcoming medical meeting and the new approach to care will be sent along to the U.S. Food and Drug Administration (FDA) and other global regulators for approval.
Camizestrant was evaluated in the phase 3 SERENA-6 trial for patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer who develop something called an ESR1 mutation. The data will be presented at an upcoming medical meeting and the new approach to care will be sent along to the U.S. Food and Drug Administration (FDA) and other global regulators for approval.
Read MoreWhy ESR1 Mutations Matter
Some HR+ breast cancers can become resistant to common hormone therapies, such as aromatase inhibitors (anastrozole or letrozole). One key reason for this resistance can be the emergence of ESR1 mutations, which affects the estrogen receptor’s structure in such a way that it no longer responds to standard treatments. This can allow the cancer to keep growing despite therapy.
“ESR1 mutations lead to changes in the estrogen receptor and are a common cause of acquired resistance to endocrine therapy,” Dr. Teplinsky explains.
Detecting these mutations early is critical because it lets doctors switch treatments quicker, ideally before the tumor shows outward signs of progression.
What Did the SERENA-6 Trial Find?
During the SERENA-6 trial, the researchers regularly tested the patient’s blood for tiny fragments of cancer DNA — specifically looking for ESR1 mutations. If these mutations show up, it signals potential drug resistance, prompting an earlier switch in therapy. This proactive approach could help slow the cancer’s advance and possibly improve long-term outcomes.
In SERENA-6, 315 patients with HR+, HER2- advanced breast cancer enrolled.
They were receiving a commonly used combination of a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) plus an aromatase inhibitor (anastrozole or letrozole) as their first-line treatment for advanced disease.
When the study began, patients underwent routine ctDNA testing (to look for cancer DNA). If the test uncovered an emerging ESR1 mutation, they were then “switched” from the aromatase inhibitor to camizestrant, while continuing the same CDK4/6 inhibitor.
Camizestrant belongs to a class of drugs called selective estrogen receptor degraders (SERDs) and is also considered a complete estrogen receptor antagonist. Unlike some older SERDs, camizestrant is taken orally, which can be more convenient than injectable options.
SERDs work by binding to the estrogen receptor (ER) in breast cancer cells and causing it to degrade. As a result, the tumor cell cannot receive estrogen signals that it needs to grow and survive. Early studies, such as SERENA-1 and SERENA-2, showed that camizestrant has promising anti-tumor activity even in tumors with ER-activating mutations.
Delaying Disease Progression
The primary measure of the trial’s success, or primary endpoint, was progression-free survival (PFS). PFS refers to how long patients can go without their cancer getting worse.
In SERENA-6, switching to camizestrant at the first signs of an emerging ESR1 mutation led to a statistically significant and clinically meaningful improvement in PFS compared with remaining on the standard aromatase inhibitor, both in combination with a CDK4/6 inhibitor. The exact PFS improvements are not yet known but eagerly awaited.
Other secondary endpoints — like time to second disease progression (PFS2) and overall survival (OS) — are not yet known.
These findings underscore a key point: proactively adjusting treatment in response to early signals of drug resistance might prolong how long patients live without their tumor growing.
The Value of a ctDNA-Guided Approach
Traditionally, doctors only switch treatments after a patient’s cancer shows clear evidence of progression on imaging scans (e.g., CT, MRI) or when symptoms worsen. However, SERENA-6 takes a much earlier approach by using ctDNA testing at routine tumor scan visits. Detecting ESR1 mutations in the blood allows clinicians to intervene sooner, potentially halting the cancer before it gains momentum. This approach could be a major step forward in personalizing therapy for breast cancer and delaying disease progression.
Safety and Tolerability
In the SERENA-6 trial, camizestrant’s safety profile was consistent with what had been observed in previous studies. When combined with any of the three CDK4/6 inhibitors, camizestrant did not raise unexpected side effects, and the rates of patients stopping treatment were low in both the investigational and the control groups.
In short, no new safety concerns emerged, suggesting this combination could be a viable option for many patients if further data continue to support its benefits.
Why This Matters to Patients
The results of the SERENA-6 trial are promising for patients for a number of reasons, including:
- Extending the Benefit of First-Line Therapy: SERENA-6 highlights an innovative way to get more mileage out of first-line therapy. Many patients rely on a CDK4/6 inhibitor plus an aromatase inhibitor to control their HR+, HER2- advanced breast cancer. However, the emergence of ESR1 mutations can cause resistance and disease progression. By switching to camizestrant at the right time, patients may enjoy a longer period without their tumor growing.
- Avoiding or Delaying Chemotherapy: One secondary endpoint in the study was chemotherapy-free survival — the period during which patients could stay on an endocrine-based approach before moving on to chemotherapy. Delaying or avoiding chemotherapy can help maintain a better quality of life, with fewer side effects such as hair loss, fatigue, and risk of infection.
- Hope for a Potential New Standard of Care: Aromatase inhibitors plus CDK4/6 inhibitors are a cornerstone of first-line therapy for many patients with advanced breast cancer. If future results continue to be positive and regulatory authorities approve camizestrant, it has the potential to become a standard-of-care option for patients with emerging ESR1 mutations. This could be an important victory in the fight against breast cancer, particularly for those whose tumors stop responding to current treatments.
Practical Tips for Patients and Families
Ask About ESR1 Mutation Testing
If you are receiving first-line therapy for HR-positive, HER2-negative breast cancer, talk to your oncologist about ESR1 mutation testing. Early detection of emerging resistance can open doors to new treatment options or clinical trials.
Stay Updated on Clinical Trials
Clinical trials often give patients access to cutting-edge therapies like camizestrant before they become widely available. Exploring these possibilities with your care team can help you make informed decisions about your treatment plan.
Maintain Open Communication
Let your doctor or nurse know about any changes in your symptoms or side effects. Early intervention — whether with supportive care or a switch in medication — can greatly improve your comfort and outcomes.
Seek Emotional and Social Support
Consider joining a support group or talking to a counselor. Living with advanced breast cancer is both physically and emotionally challenging. Family, friends, therapists, and fellow patients can be invaluable in helping you cope.
Focus on Self-Care
Engage in gentle activities like walking, yoga, or meditation to reduce stress and maintain strength. Nutrition and rest are equally important. Looking after your overall health can help you face cancer treatment with more resilience.
Questions To Ask Your Doctor
- Am I eligible for camizestrant?
- Is there a clinical trial I should consider enrolling in?
- What are the risks vs. benefits of camizestrant compared to other approaches?
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