News
Ado-trastuzumab emtansine, a HER-2 targeted antibody-drug conjugate, has been approved by the Food and Drug Administration for treatment of women with HER2-positive, late-stage metastatic breast cancer, the agency announced Feb. 22.
Marketed as Kadcyla by Genentech, the treatment is a combination of an HER2-targeted antibody, trastuzumab, and DM1, a microtubule inhibitor, and is indicated as a single agent "for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination," according to the prescribing information. Patients should have either received previous therapy for metastatic disease, or had disease recurrence during or within 6 months of completing adjuvant therapy, according to the indication. The treatment is administered in an intravenous infusion every 3 weeks.
"Kadcyla is trastuzumab connected to a drug called DM1 that interferes with cancer cell growth," Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, said in a statement. "Kadcyla delivers the drug to the cancer site to shrink the tumor, slow disease progression, and prolong survival," he added.
Kadcyla is the fourth FDA-approved breast cancer treatment that targets the HER2 protein. The other three drugs approved for treating HER2-positive breast cancer are trastuzumab (Herceptin), approved in 1998; lapatinib (Tykerb), approved in 2007; and pertuzumab (Perjeta), approved in 2012.
Approval of Kadcyla was based on a randomized, open label, phase III study of 991 patients with HER2-positive, locally-advanced breast cancer or metastatic breast cancer who had previously been treated with trastuzumab and a taxane chemotherapy. The median progression-free survival was 9.6 months among those treated with Kadcyla, compared with 6.4 months in patients treated with lapatinib plus capecitabine. The median overall survival was 30.9 months among those treated with Kadcyla, compared with 25.1 months among those treated with lapatinib and capecitabine, according to statements from the FDA and Genentech. Overall survival and progression-free survival were the study’s primary endpoints.
The most common side effects associated with treatment (affecting more than 25% of patients) were fatigue, nausea, musculoskeletal pain, thrombocytopenia, headache, increased transaminases, and constipation.
This accelerated approval was completed in 6 months instead of the usual 12-month review period, which is used for drugs that may provide safer and effective treatment when there is no satisfactory alternative treatment or when the treatment provides significant improvements over available treatments. Ado-trastuzumab emtansine has been referred to as T-DM1 during clinical trials.
Kadcyla will be available within 2 weeks of approval, according to the statement from Genentech, a member of the Roche group. The agent is currently under review by the European Medicines Agency for the same indication.
Serious adverse events associated with Kadcyla should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch. The prescribing information is available at www.accessdata.fda.gov/drugsatfda_docs/label/2013/125427lbl.pdf.
