FDA approves new breast cancer drug that spares healthy cells
On February 22, the Food and Drug Administration announced that it had approved Kadcyla (ado-trastuzumab emtansine) as a new therapy for patients with HER2-positive, late-stage (metastatic) breast cancer. An advantage of Kadcyla is that it is less harmful to normal cells; however, major side-effects can occur.
The FDA explains that HER2 is a protein involved in normal cell growth. It is found in increased amounts in some types of cancer cells (HER2-positive), including some breast cancers. In these HER2-positive breast cancers, the increased amount of the HER2 protein contributes to cancer cell growth and survival. The agency notes that Kadcyla, which is marketed Roche’s Genentech unit, is intended for patients who were previously treated with trastuzumab, another anti-HER2 therapy, and taxanes, a class of chemotherapy drugs commonly used for the treatment of breast cancer. The downside of this new medication is its cost. According to Genentech, Kadcyla will cost $9,800 per month, compared to $4,500 per month for regular Herceptin. The company estimates a full course of Kadcyla, about nine months of medicine, will cost $94,000. Thus, the cost of the drug is beyond the reach of many women unless they have an insurance plan.
“Kadcyla is trastuzumab connected to a drug called DM1 that interferes with cancer cell growth,” explained Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. He added, “Kadcyla delivers the drug to the cancer site to shrink the tumor, slow disease progression and prolong survival. It is the fourth approved drug that targets the HER2 protein.”
Kadcyla was reviewed under the FDA’s priority review program, which provides for an expedited six-month review of drugs that may provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to marketed products. Other FDA-approved drugs used to treat HER2-positive breast cancer include trastuzumab (1998), lapatinib (2007) and pertuzumab (2012). The safety and effectiveness of Kadcyla were evaluated in a clinical study of 991 patients randomly assigned to receive Kadcyla or another chemotherapy regimen: lapatinib plus capecitabine. The study was designed to measure progression-free survival, the length of time patients lived without the cancer progressing, and overall survival, the length of time patients lived before death. The subjects received treatment until either the cancer progressed or the side effects became intolerable.
The investigators found that patients treated with Kadcyla had a median progression-free survival of 9.6 months compared to 6.4 months in patients treated with lapatinib plus capecitabine. The median overall survival was 30.9 months in the Kadcyla group and 25.1 months in the lapatinib plus capecitabine group.
In addition to its high cost, Kadcyla is associated with significant side-effects. The FDA notes that the medication is being approved with a Boxed Warning alerting patients and healthcare professionals that the drug can cause liver toxicity, heart toxicity and death. The medication can also cause severe life-threatening birth defects; therefore, the FDA cautions that pregnancy status should be verified prior to starting Kadcyla treatment. Beyond the serious side effects, 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.
According to the National Cancer Institute, breast cancer is the second leading cause of cancer-related death among women. An estimated 232,340 women will be diagnosed with breast cancer, and 39,620 will die from the disease in 2013. Almost 20% of breast cancers have increased amounts of the HER2 protein.