FDA Approves Breast Cancer Treatment Guided by a Mutation
The Food and Drug Administration (FDA) granted accelerated approval to ETCAMAH (camizestrant), an oral treatment developed by the pharmaceutical company AstraZeneca, for a specific group of patients with advanced or metastatic breast cancer. This medication is indicated for adult patients with hormone-sensitive, HER2-negative breast cancer when an ESR1 gene mutation is detected during treatment with hormonal therapy and a CDK4/6 inhibitor. There are different options available to treat this type of breast cancer, but one problem that can arise is that the tumor develops resistance to hormonal therapy. Mutations in the ESR1 gene are among the causes of this resistance.
When breast cancer is HER2-negative, it means that the cancer cells do not have high levels of the HER2 protein. HER2 stands for human epidermal growth factor receptor 2 and is a protein involved in cell growth and division. When excessive amounts of HER2 are present, cells can grow and multiply more rapidly, a characteristic of HER2-positive tumors. HER2 status is different from hormone receptor status, which indicates whether cancer cells use hormones such as estrogen or progesterone to grow.
The ESR1 gene contains the instructions for producing the estrogen receptor, a protein that allows cells to respond to this hormone. Some mutations in this gene can allow the cancer to continue using estrogen receptor signals despite treatment, reducing the effectiveness of certain hormonal medications. One of the novel aspects of this approval is that the mutation can be identified through small fragments of DNA released by the tumor that circulate in the blood. The FDA also approved the Guardant360 CDx test to identify patients with this mutation who may receive camizestrant.
This blood test makes it possible to detect signs of resistance before imaging studies show that the cancer is progressing. According to the FDA, this is the first approval of a cancer treatment guided by the detection of a resistance mutation in the blood before imaging demonstrates disease progression. In this way, doctors can modify treatment when signs appear that the tumor is developing resistance, without necessarily having to wait until its progression becomes visible on imaging. This makes it possible to intervene at an earlier stage in the process.
The effectiveness of camizestrant was evaluated in the SERENA-6 clinical trial, which included patients with this type of breast cancer who were receiving hormonal therapy together with a CDK4/6 inhibitor and in whom an ESR1 mutation was detected without evidence of disease progression on imaging. One group of patients switched from hormonal therapy to camizestrant, while the other group continued with the treatment they had been receiving. The CDK4/6 inhibitor was continued in both groups. The results showed a 56% reduction in the risk of disease progression or death in the group treated with camizestrant.
Progression-free survival, which measures how long a patient remains without the disease worsening, was 16 months with camizestrant, compared with 9.2 months among those who continued their previous hormonal therapy. At the time of the analysis, overall survival data were not yet definitive. The recommended dose of camizestrant is 75 mg taken orally once daily, with or without food, until the disease progresses or adverse effects make it necessary to discontinue treatment. It is administered in combination with a CDK4/6 inhibitor, which may be abemaciclib, palbociclib, or ribociclib.
As with other cancer treatments, the combination of camizestrant with a CDK4/6 inhibitor can cause adverse effects. Among the most common are changes in certain blood cell counts, visual disturbances, and fatigue. The prescribing information also includes warnings related to a decreased heart rate and the risk of abnormal heart rhythms, particularly when combined with certain medications. For this reason, treatment should be administered under medical supervision, taking into account the other medications the patient is receiving.
Camizestrant received accelerated approval based on the results available to date. This mechanism allows the FDA to authorize certain medications for serious diseases when the available evidence can reasonably predict a potential clinical benefit while additional information is being collected. In the case of camizestrant, continued approval for this indication will depend on subsequent studies confirming that benefit. These studies will also provide more precise information about the treatment’s effect on long-term survival.
The review was conducted under Project Orbis, an initiative of the FDA’s Oncology Center of Excellence that allows cancer drugs to be submitted and reviewed simultaneously by international regulatory agencies. In this case, the FDA collaborated with regulatory agencies in Australia, Brazil, Canada, Singapore, and Switzerland, although evaluations may continue independently in some of these countries. The application was also discussed by the Oncology Drugs Advisory Committee, and the Assessment Aid, a voluntary submission designed to facilitate the FDA’s evaluation, was used. Camizestrant received standard review and had previously been granted Breakthrough Therapy designation.
The approval of camizestrant provides a new option for patients whose breast cancer is beginning to develop resistance to hormonal treatment. Beyond introducing a new medication, the ability to detect changes in the tumor through a blood test may help guide treatment decisions before the disease shows progression on imaging. Subsequent studies will provide more information about the long-term benefits of this strategy.
Viviana Cetola
Life News Today
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