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FDA expands Kadcyla approval for adjuvant breast cancer therapy
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The FDA expanded the approval of ado-trastuzumab emtansine to include adjuvant treatment of individuals with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant treatment with trastuzumab and taxane chemotherapy.
Ado-trastuzumab emtansine (Kadcyla, Genentech) is an antibody-drug conjugate that combines the HER2-targeting agent trastuzumab (Herceptin, Genentech) with the chemotherapy agent DM1. The agent already had been approved to treat patients with metastatic HER2-positive breast cancer who underwent prior treatment with trastuzumab and taxane chemotherapy.
The FDA approved the new indication through its real-time oncology review pilot program, designed to create a more efficient process to ensure effective and safe treatments are made available to patients as early as possible. The agency — which had granted breakthrough therapy designation to ado-trastuzumab emtansine for this indication — granted the approval 12 weeks after completion of the application submission.
“This approval is a significant treatment advance for HER2-positive early breast cancer,” Sandra Horning, MD, chief medical officer and head of global product development at Genentech, said in a company-issued press release. “With every step forward in reducing the risk [for] disease recurrence, we come closer to the goal of helping each person with early breast cancer have the greatest opportunity for cure.”
The FDA based the new indication on results of the randomized phase 3 KATHERINE study, which included 1,486 patients with HER2-positive early breast cancer who had pathologic invasive residual disease in the breast or axillary lymph nodes after neoadjuvant therapy that included trastuzumab and taxane-based chemotherapy.
Researchers randomly assigned half of the patients to ado-trastuzumab emtansine dosed at 3.6 mg/kg via IV every 3 weeks. The other half received trastuzumab (Herceptin, Genentech) 6 mg/kg via IV every 3 weeks for 14 cycles.
Invasive DFS — defined as the time from randomization free from invasive breast cancer recurrence or death from any cause — served as the primary endpoint.
Results showed ado-trastuzumab reduced by half the risk for invasive breast cancer recurrence or death from any cause (HR = 0.5; 95% CI, 0.39-0.64). Researchers reported 3-year invasive DFS rates of 88.3% in the ado-trastuzumab emtansine group and 77% in the trastuzumab group.
A higher percentage of patients assigned ado-trastuzumab emtansine experienced grade 3 or higher adverse events (26% vs. 15%), the most common of which were thrombocytopenia (6% vs. 0.3%) and hypertension (2% vs. 1.2%).
The most common side effects reported in the ado-trastuzumab emtansine group included fatigue, nausea, increased blood levels of liver enzymes, musculoskeletal pain, bleeding, decreased platelet count, headache, numbness, tingling or pain in the feet or hands, or joint pain.