Genentech announced the FDA has expanded the approval of Kadcyla (ado-trastuzumab emtansine) to include the adjuvant (after surgery) treatment of people with HER2-positive early breast cancer (EBC) who have residual invasive disease after neoadjuvant (before surgery) taxane and Herceptin (trastuzumab)-based treatment.
The FDA rapidly reviewed and approved the application under the FDA’s Real-Time Oncology Review (RTOR) and Assessment Aid pilot programs, leading to an approval 12 weeks after completing the submission. Kadcyla was also granted Breakthrough Therapy Designation for this indication.
The FDA approval for this indication was based on results of the Phase III KATHERINE study. Results showed Kadcyla significantly reduced the risk of invasive breast cancer recurrence or death from any cause (invasive disease-free survival; iDFS) by 50% compared to Herceptin as an adjuvant treatment in patients with HER2-positive EBC who have residual invasive disease after neoadjuvant taxane and Herceptin-based treatment. At three years, 88.3% of patients treated with Kadcyla did not have their breast cancer return compared to 77.0% treated with Herceptin, an absolute improvement of 11.3%. The most common Grade 3 or higher side effects (>2%) with Kadcyla in the KATHERINE study were decreased platelet count and high blood pressure. The most common side effects (>25%) with Kadcyla were fatigue; nausea; increased blood levels of liver enzymes; musculoskeletal pain; bleeding; decreased platelet count; headache; numbness, tingling or pain in the hands or feet; and joint pain.
Kadcyla was previously approved by the FDA in 2013 for patients with HER2-positive, late-stage (metastatic) breast cancer.
About HER2-positive breast cancer
Breast cancer is one of the most common cancers among women worldwide. According to the American Cancer Society, approximately 271,000 people in the United States will be diagnosed with breast cancer, and more than 42,000 will die from the disease in 2019. Breast cancer is not one, but many diseases based on the biology of each tumor. In HER2-positive breast cancer, there is excess HER2 protein on the surface of tumor cells. Approximately 15-20% of breast cancers are HER2-positive based on the result of a diagnostic test.
The goal in treating EBC is to provide people with the best chance for a cure, which may involve treatment before and after surgery as part of a comprehensive treatment approach. Neoadjuvant treatment is given before surgery with the goal of shrinking tumors and helping to improve surgical outcomes. Patients who have residual disease after neoadjuvant treatment have a worse prognosis than those with no detectable disease.
Kadcyla is an antibody-drug conjugate (ADC) engineered to deliver potent chemotherapy directly to HER2-positive cancer cells. It is designed to limit damage to healthy tissues, although it can still affect them. It combines two anti-cancer agents using a stable linker: the HER2-targeting trastuzumab (the active ingredient in Herceptin) and the chemotherapy agent DM1.
In the U.S., Genentech licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.