Arimidex and Faslodex Combined Show Promise in Metastatic Breast Cancer

The combination of anastrozole (ArimidexR) and fulvestrant (FaslodexR) prolonged overall survival and progression-free survival in postmenopausal women with previously untreated hormone receptor-positive metastatic breast cancer compared to Arimidex alone, according to the results of a study published in the New England Journal of Medicine. ?

Each year roughly 200,000 U.S. women are diagnosed with breast cancer. Many of these breast cancers are hormone receptor-positive, meaning that they are stimulated to grow by the circulating female hormones estrogen and/or progesterone. Treatment of hormone receptor-positive breast cancer often involves hormonal therapies that suppress or block the action of estrogen.?

Arimidex is a type of hormone therapy known as an aromatase inhibitor and works by suppressing the production of estrogen in postmenopausal women. Faslodex is a type of hormonal therapy known as an estrogen receptor antagonist and works by binding to estrogen receptors and degrading them. Both drugs are approved for the treatment of postmenopausal women with metastatic breast cancer. ?

To evaluate the drugs in combination, researchers conducted a trial involving 694 women who were randomly assigned to receive Arimidex alone or Arimidex and Faslodex combined. All women in the study had cancer that was hormone-receptor positive and none of them had been previously treated with chemotherapy, immunotherapy, or hormone therapy to stop the spread of disease. ?

The results indicated that the combination was superior to the single agent therapy. The median progression-free survival was 15 months in the combination group, compared to 13.5 months in the Arimidex alone group. Overall survival was also longer in the combination group—47.7 months compared to 41.3 months in the single agent group. Of note, not all patients assigned to anastrozole subsequently received fulvestrant.? Furthermore, another study looking at the combination of anastrozole and fulvestrant failed to show superiority over anastrozole alone.?

Both groups had mild to moderate side effects such as joint pain and hot flashes. Although the rate was higher in the combination group, it was not statistically significant. ?

The researchers concluded that the combination of Arimidex and Faslodex was superior to Arimidex alone for the treatment of hormone-receptor positive metastatic breast cancer—even though the dose of Faslodex was below the current standard dose. However, the results of this study have to be reconciled with the less favorable results from the other study that evaluated this combination. ?Many oncologists continue to believe that the optimal hormonal therapy approach for women newly diagnosed with metastatic breast cancer remains uncertain.?

Reference:?

Mehta RS, Barlow WE, Albain KS, et al. Combination anastrozole and fulvestrant in metastatic breast cancer. New England Journal of Medicine. 2012; 367:435-444.?

Posted August 6, 2012

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Cabozantinib Shows Promise against Bone Metastases

The investigational drug cabozantinib is showing promise against several types of advanced cancer, and may also reduce or eliminate bone metastases (cancer that has spread to the bone) in some patients. These results will be presented at the 2011 annual meeting of the American Society of Clinical Oncology.?

Metastatic cancer refers to cancer that has spread to distant sites in the body. Several types of cancer—including cancers of the prostate, lung, and breast—have a tendency to spread to the bone. Bone metastases can lead to serious problems such as fracture and spinal cord compression, and may require treatment with surgery or radiation therapy. ?

Cabozantinib is an investigational drug that targets two proteins—MET and VEGFR2—that play a role in the development and progression of many types of cancer. ?

To evaluate cabozantinib in the treatment of advanced cancer, researchers conducted a Phase II clinical trial among 398 patients. The nine types of cancer included in the study were breast, stomach/gastroesophageal junction, non-small cell lung, ovarian, pancreatic, hormone-refractory prostate, small cell lung, liver, and melanoma. At the start of the study, 39% of the patients had bone metastases.?

Patients were initially treated with 12 weeks of cabozantinib. After 12 weeks, patients who had a partial response to treatment (a reduction in detectable cancer) remained on cabozantinib, patients with stable disease (no significant change in the cancer) were randomly assigned to either continue with cabozantinib or to take a placebo, and patients with progressive (worsening) cancer were withdrawn from the study.?

By week 12, 9% of patients responded to treatment. ?For some types of cancer, cabozantinib produced high disease control rates (defined as either a reduction in cancer or stable disease). The disease control rates were 76% for liver cancer, 71% for prostate cancer, and 58% for ovarian cancer.?Among the 68 patients with bone metastases, 59 had partial or complete disappearance of the cancer on bone scans, often accompanied by significant pain relief. A majority of these patients had hormone-refractory prostate cancer, but patients with breast cancer and melanoma also experience a disappearance of bone metastases. The researchers had not expected this result.?The most common side effects were fatigue and hand-foot syndrome (pain, swelling, numbness, tingling, or redness of the hands or feet).?

In a prepared statement, the lead author of the study noted “Cabozantinib appears to have significant effects on several treatment-resistant tumors, as well as impressive effects on bone metastases. In addition, these effects are associated with rapid improvement in pain, a reduction in opiate narcotic requirements and improvement in anemia. The implications of these results are very exciting—it is unusual to find a targeted therapy, absent of a molecular mutation in tumors, that works in bony disease and has this activity.”?

Research on cabozantinib continues. ?

Reference: Gordon MS, Vogelzang NJ, Schoffski P et al. Cabozantinib (XL184) has activity in both soft tissue and bone: Results of a phase II randomized discontinuation trial (RDT) in patients (pts) w/ advanced solid tumors. Paper presented at: 2011 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract 3010.?

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