FDA Approves T-DM1 (Kadcyla) for HER2-Positive Breast Cancer

February 22, 2013

The FDA has approved ado-trastuzumab emtansine (Kadcyla), known as T-DM1 in development, for the treatment of women with metastatic HER2-positive breast cancer.

The US Food and Drug Administration (FDA) approved ado-trastuzumab emtansine (Kadcyla) for the treatment of patients with metastatic HER2-positive breast cancer earlier today. HER2-positive disease accounts for nearly 20% of all breast cancers.

The new drug, known as T-DM1 during clinical research, is intended for patients whose disease has progressed following treatment with trastuzumab (Herceptin) and a taxane.

“Kadcyla is trastuzumab connected to a drug called DM1 that interferes with cancer cell growth,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a press release. “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.”

Most recently the FDA approved pertuzumab (2012) for HER2-positive breast cancer-trastuzumab (1998) and lapatinib (2007) are also FDA-approved for this indication.

The trial that led to the approval of ado-trastuzumab emtansine, the phase III EMILIA trial, was an open-label trial that included 991 patients. Patients were randomized to receive ado-trastuzumab emtansine at a dose of 3.6 mg/kg every 3 weeks or lapatinib (Tykerb) plus capecitabine. Primary endpoints of the trial were progression-free and overall survival.

Patients who received ado-trastuzumab emtansine had a median progression-free survival of 9.6 months compared with 6.4 months for patients treated with lapatinib plus capecitabine (P < .0001). The median overall survival was 30.9 months in the ado-trastuzumab emtansine arm of the trial, compared with 25.1 months for patients in the lapatinib plus capecitabine arm.

Ado-trastuzumab emtansine was well tolerated, with the most common adverse events being nausea, fatigue, pain in the muscles or joints, headache, and constipation. Common high-grade toxicities included thrombocytopenia (12.9%) and elevation in liver function test, though both were resolved when treatment was temporarily halted.

The new drug carries a boxed warning alerting patients and health care professionals that ado-trastuzumab emtansine can cause reductions in left ventricular ejection fraction, liver toxicity, and death. The drug can also cause severe birth defects, so a patient's pregnancy status should be determined prior to treatment.