- Roche’s application is being reviewed under the US FDA's Real-Time Oncology Review and Assessment Aid pilot programmes
- Kadcyla was granted Breakthrough Therapy Designation for this application
Roche today announced completing the submission of a supplemental Biologics License Application to the US Food and Drug Administration (FDA) for Kadcyla (trastuzumab emtansine) for adjuvant (after surgery) treatment of people with HER2-positive early breast cancer (eBC) with residual disease after neoadjuvant (before surgery) treatment. The FDA is reviewing the application under the Real-Time Oncology Review and Assessment Aid pilot programmes, which aim to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.[1,2] 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.
“Kadcyla was granted Breakthrough Therapy Designation and is also the first Roche medicine to be reviewed under the FDA’s Real-Time Oncology Review pilot programme; both FDA initiatives aim to expedite reviews and bring medicines to patients sooner” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “We are working closely with the FDA to bring Kadcyla to people with HER2-positive early breast cancer who have residual disease after neoadjuvant therapy as early as possible.”
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; iDFS) by 50% (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% of people 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 3-4 side effects (>1%) with Kadcyla in the KATHERINE study were decreased platelet count; high blood pressure; radiation-induced skin injury; numbness, tingling or pain in the hands or feet; decreased neutrophil count; low blood potassium level; fatigue and decrease in red blood cells.
About the KATHERINE study
KATHERINE is an international, multi-centre, two-arm, randomised, 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 randomisation 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 (ADC) engineered to deliver potent chemotherapy directly to HER2-positive cancer cells, potentially limiting damage to healthy tissues.[6,7] It combines two anti-cancer properties joined together by a stable linker: the HER2-targeting properties of trastuzumab (the active ingredient in Herceptin) and the chemotherapy agent DM1. Kadcyla is the only ADC approved as a single agent in 104 countries including the US and EU for the treatment of people with HER2-positive metastatic breast cancer who have previously received Herceptin and taxane chemotherapy, separately or in combination. Roche licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.
About Roche’s medicines for HER2-positive breast cancer
Roche has been leading research into the HER2 pathway for over 30 years and is committed to improving the health, quality of life and survival of people with both early and advanced HER2-positive disease. HER2-positive breast cancer is a particularly aggressive form of the disease that affects approximately 15-20% of patients. Roche has developed three innovative medicines that have helped transform the treatment of HER2-positive breast cancer: Herceptin (trastuzumab), Perjeta (pertuzumab) and Kadcyla (trastuzumab emtansine). Eligibility for treatment with Roche’s HER2-targeted medicines is determined via a diagnostic test, which identifies people who will likely benefit from these medicines at the onset of their disease.