Genentech has submitted a supplemental Biologics License Application to the FDA for Kadcyla (ado-trastuzumab emtansine) for adjuvant treatment of people with HER2-positive early breast cancer with residual disease after neoadjuvant treatment.
Genentech is a member of the Roche Group.
The FDA is reviewing the application under the Real-Time Oncology Review and Assessment Aid pilot programs, which aim to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.
For this indication, Kadcyla was also granted Breakthrough Therapy Designation, which is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases.
This application is based on results of the phase III KATHERINE study showing Kadcyla significantly reduced the risk of invasive breast cancer recurrence or death from any cause (invasive disease-free survival) by 50 percent (HR=0.50, 95% CI 0.39-0.64, p<0.0001) compared to Herceptin (trastuzumab) as an adjuvant treatment in people with HER2-positive EBC who have residual disease present following neoadjuvant treatment.
People who have residual disease after neoadjuvant treatment have a worse prognosis than those with no detectable disease. At three years, 88.3 percent of people treated with Kadcyla did not have their breast cancer return compared to 77.0 percent treated with Herceptin, an absolute improvement of 11.3 percent.
KATHERINE is an international, multi-center, two-arm, randomized, open-label, Phase III study evaluating the efficacy and safety of Kadcyla versus Herceptin as an adjuvant therapy in people with HER2-positive EBC who have pathological invasive residual disease in the breast and/or axillary lymph nodes following neoadjuvant therapy that included Herceptin and taxane-based chemotherapy.
The primary endpoint of the study is iDFS, which in this study is defined as the time from randomization free from invasive breast cancer recurrence or death from any cause. Secondary endpoints include disease-free survival and overall survival.
Kadcyla is an antibody-drug conjugate engineered to deliver potent chemotherapy directly to HER2-positive cells. It is designed to limit damage to healthy tissues, although it can still affect them. Kadcyla can cause serious side effects.
It combines two anti-cancer agents using a stable linker: the HER2-targeting trastuzumab (the active ingredient in Herceptin) and the chemotherapy agent DM1. Kadcyla is the only ADC approved for the treatment of HER2-positive metastatic breast cancer. In the U.S., Genentech licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.
Kadcyla, as a single agent, is indicated for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either:
Received prior therapy for metastatic disease, or
Developed disease recurrence during or within six months of completing adjuvant therapy.
