Afinitor Delays Progression of Advanced Breast Cancer

Among postmenopausal women with advanced breast cancer that had become resistant to hormonal therapy, the combination of AfinitorR (everolimus) and AromasinR (exemestane) delayed cancer progression to a greater extent than Aromasin alone. The results of this Phase III clinical trial were presented at the 2011 European Multidisciplinary Cancer Congress.???

Each year roughly 200,000 U.S. women are diagnosed with breast cancer. Many of these breast cancers are hormone receptor-positive, meaning that exposure to estrogen and/or progesterone can cause them to grow.?

Treatment of hormone receptor-positive breast cancer often includes hormonal therapies such as tamoxifen or an aromatase inhibitor. Tamoxifen acts by blocking estrogen receptors, and aromatase inhibitors suppress the production of estrogen in postmenopausal women. Aromatase inhibitors include FemaraR (letrozole), ArimidexR (anastrozole), and AromasinR (exemestane). Many women with advanced breast cancer become resistant to hormonal therapy, and treatment options for these women remain limited.???

Afinitor is an oral medication that works by inhibiting a protein known as mTOR. The mTOR protein plays an important role in regulating cancer cell division and blood vessel growth.?Currently, Afinitor is used for the treatment of selected patients with kidney cancer, pancreatic neuroendocrine tumors, and subependymal giant cell astrocytoma (SEGA).??

To explore the use of Afinitor among women with advanced, estrogen receptor-positive, HER2-negative breast cancer, researchers conducted a Phase III clinical trial (BOLERO-2) among 724 women. All of the women had experienced cancer recurrence or progression in spite of treatment with Femara or Arimidex. Study participants were treated with Aromasin alone or in combination with Afinitor.???

Survival without cancer progression was 6.9 months among women treated with both Afinitor and Aromasin, compared with 2.8 months among women treated with Aromasin alone.?The most common serious side effects in the Afinitor group were stomatitis (inflammation of the lining of the mouth; 7.7%), anemia (5.8%), shortness of breath (3.9%), hyperglycemia (4.3%), fatigue (3.7%) and pneumonitis (lung inflammation; 3.1%), and elevated liver enzymes (3.1%). ?

These results suggest that the addition of Afinitor to Aromasin improved outcomes among women with advanced breast cancer that had previously been treated with hormonal therapy. Afinitor has not yet been approved for use in breast cancer.???

Reference: Baselga J, Campone M, Sahmoud T et al. Everolimus in combination with exemestane for postmenopausal women with advanced breast cancer who are refractory to letrozole or anastrozole: results of the BOLERO-2 phase III trial. Presented at the 2011 European Multidisciplinary Cancer Conference. Stockholm, Sweden. September 23-27, 2011. Abstract LBA9. ?

Posted September 30, 2011

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Adding Afinitor to Herceptin May Provide Breast Cancer Benefit

For women with HER2-positive breast cancer that worsens in spite of treatment with HerceptinR (trastuzumab), treatment with a combination of Herceptin and AfinitorR (everolimus) may provide a benefit. These results were published in the Journal of Clinical Oncology.????

Approximately 20-25% of breast cancers overexpress (make too much of) the HER2 protein. HER2-targeted therapies such as Herceptin have dramatically improved outcomes for women with HER2-positive breast cancer, but researchers continue to explore new approaches to treatment. One important focus of research is the treatment of cancer that has progressed after prior HER2-targeted therapy.???

Afinitor is an oral medication that works by inhibiting a protein known as mTOR. The mTOR protein plays an important role in regulating cancer cell division and blood vessel growth.?Currently, Afinitor is used for the treatment of selected patients with kidney cancer, pancreatic neuroendocrine tumors, and subependymal giant cell astrocytoma (SEGA).?

To evaluate the combination of Herceptin and Afinitor, researchers combined information from two clinical trials that were conducted concurrently. Information was available for 47 women with HER2-positive metastatic breast cancer that had progressed during treatment with Herceptin. Study participants received Herceptin every three weeks in combination with daily Afinitor.????

Seven patients (15%) had a partial response to treatment (a reduction in detectable cancer).?An additional nine patients (19%) experienced stable disease for six months or longer. ?Median duration of survival without cancer progression was 4.1 months.?Side effects included fatigue, infection, and mouth sores (mucositis).?

These results suggest that the combination of Afinitor and Herceptin may benefit women with HER2-positive, advanced breast cancer that has worsened in spite of Herceptin treatment. Afinitor has been approved by the US Food and Drug Administration for other purposes, but has not yet been approved for breast cancer. At this time, the use of Afinitor would only be appropriate for women with ?HER2-positive breast cancer in the setting of a clinical trial.? Additional, ongoing studies are evaluating the combination of Herceptin, Afinitor, and chemotherapy in the first- and second-line treatment of metastatic breast cancer. ?

Reference: Khanh Morrow P, Wulf GM, Ensor J et al. Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy. Journal of Clinical Oncology. Early online publication July 5, 2011.?

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