Lapatinib Approved for Initial Treatment of Metastatic Breast Cancer

The U.S. Food and Drug Administration (FDA) has expanded its approval of lapatinib (TykerbR) to include initial treatment of metastatic, postmenopausal breast cancer that is both HER2-positive and hormone receptor-positive. In this setting, lapatinib is approved for use in combination with the aromatase inhibitor drug letrozole (FemaraR).

Twenty to thirty percent of breast cancers overexpress (make too much of) a protein known as HER2. Overexpression of this protein leads to increased growth of cancer cells. Fortunately, the development of treatments that specifically target HER2-positive cells has improved outcomes among women with HER2-positive breast cancer. Drugs that target HER2 include trastuzumab (HerceptinR) and lapatinib.

Lapatinib was initially approved in 2007 for use in combination with the chemotherapy drug capecitabine (XelodaR) for the treatment of HER2-positive advanced or metastatic breast cancer that has progressed following prior therapy with an anthracycline, a taxane, and trastuzumab.

The expansion of lapatinib’s approval to include the initial treatment of metastatic breast cancer was based on a study in 219 postmenopausal women with HER2-positive, hormone receptor-positive, metastatic breast cancer. Women were treated with either letrozole alone or letrozole plus lapatinib. Both drugs are given orally.

Progression-free survival was 5.2 months longer among women treated with letrozole and lapatinib than among women treated with letrozole alone.

The most common side effects of lapatinib include diarrhea, rash, nausea, and fatigue.

Reference: FDA News Release. FDA expands use of approved breast cancer drug. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm199374.htm. Accessed February 1, 2010.

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Xgeva Approved for Patients with Bone Metastases

Xgeva? (denosumab) has been approved by the US Food and Drug Administration (FDA) for the prevention of bone complications such as fracture in patients with bone metastases from solid (not blood-related) cancers. It is not approved for patients with multiple myeloma or other cancers of the blood.

Metastatic cancer refers to cancer that has spread to distant sites in the body. Several types of cancer 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.

Denosumab is a drug that targets a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). Denosumab was initially approved under the trade name ProliaR for the treatment of osteoporosis in postmenopausal women; it is now also approved under the trade name Xgeva for patients with bone metastases. Xgeva is administered using a higher dose and with more frequent dosing than Prolia.

The safety and efficacy of Xgeva were established in three clinical trials that compared Xgeva to the bisphosphonate drug ZometaR (zoledronic acid). One of the studies enrolled patients with breast cancer, one enrolled patients with prostate cancer, and the third enrolled patients with a variety of cancer types.

The studies assessed the frequency and timing of bone complications (“skeletal related events”). The bone complications that were evaluated were fracture, radiation to the bone, surgery to the bone, and spinal cord compression. In the studies of breast and prostate cancer patients, Xgeva delayed bone complications to a greater extent than Zometa. In the study of patients with other cancer types, Xgeva and Zometa produced similar results.

The approval of Xgeva expands the treatment options available to patients with bone metastases.

Reference:? US Food and Drug Administration news release. FDA approves Xgeva to help prevent cancer-related bone injury. November 19, 2010.

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Kadcyla Approved for HER2-Positive Metastatic Breast Cancer

The U.S. Food and Drug Administration (FDA) has approved Kadcyla? (ado-trastuzumab emtansine, formerly known as T-DM1) for the treatment of HER2-positive, metastatic breast cancer that has been previously treated with HerceptinR (trastuzumab) and taxanes, a class of chemotherapy drugs commonly used to treat breast cancer. ?

HER2 is a protein involved in normal cell growth. Approximately 20-25% of breast cancers overexpress (make too much of) the HER2 protein, and this over-expression contributes to cancer cell growth and survival. 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.?

Kadcyla combines Herceptin and a chemotherapy drug (DM1) that interferes with cancer cell growth. Kadcyla delivers Herceptin and DM1 directly to HER2-positive cells, and limits exposure of the rest of the body to the chemotherapy.?

The approval of Kadcyla was based on a clinical study that included 991 patients who were randomly assigned to receive Kadcyla or TykerbR (lapatinib) plus XelodaR (capecitabine). Patients received treatment until cancer progressed or side effects became intolerable. The study was designed to measure progression-free survival and overall survival.?

Results indicated that patients treated with Kadcyla had a median progression-free survival of 9.6 months compared to 6.4 months in patients treated with Tykerb/Xeloda. The median overall survival was 30.9 months in the Kadcyla group and 25.1 months in the Tykerb/Xeloda group.?

The most common side effects reported in patients treated with Kadcyla were nausea, fatigue, pain in the muscles or joints, low levels of platelets in the blood (thrombocytopenia), increased levels of liver enzymes, headache, and constipation.?

Kadcyla was approved under the FDA’s Priority Review Program, which allows an expedited six-month review of drugs that may offer major advances in treatment. Kadcyla will carry a Boxed Warning alerting patients and healthcare professionals that the drug can cause liver toxicity, heart toxicity, and death. The drug can also cause severe life-threatening birth defects, so pregnancy status should be verified prior to intiating Kadcyla treatment.?

Reference:?

FDA approves new treatment for late-stage breast cancer. [FDA News Release]. U.S. Food and Drug Administration website. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm340704.htm?

Posted March 20, 2013?

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