KADCYLA: KATHERINE clinical trial design
A Phase III, randomized, multicenter, open-label trial of patients with HER2+ EBC who had residual invasive disease in the breast and/or axillary lymph nodes following neoadjuvant treatment with taxane + Herceptin® (trastuzumab)-based therapy.1,2
Administered every 3 weeks for a total of 14 cycles or until recurrence, withdrawal of consent, or unmanageable toxicity.
A loading dose of 8 mg/kg of Herceptin was administered if more than 6 weeks had elapsed since the previous dose of Herceptin.
Patients received radiotherapy and/or hormonal therapy concurrent with study treatment as per local guidelines.
Randomization was stratified by clinical stage at presentation, hormone receptor status, pre-operative HER2-directed therapy (Herceptin or Herceptin + additional HER2-directed agent/s), and pathological nodal status evaluated after pre-operative therapy.1
- Primary endpoint: Invasive disease-free survival (iDFS), defined as the time from randomization to first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence, ipsilateral local or regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, or death from any cause
- Select secondary efficacy endpoints: iDFS including second primary non-breast cancer, disease-free survival (DFS), and overall survival (OS)
Key KATHERINE eligibility criteria1,3
*Using Ventana's PATHWAY anti-HER2/neu (4B5)
Rabbit Monoclonal Primary Antibody or INFORM HER2 Dual ISH DNA Probe
†If pathological examination demonstrates tumor at the line of resection (R1), additional operative procedures should be performed to obtain clear margins (R0). If tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible.3
‡If pre-chemotherapy LVEF was not assessed, the screening LVEF must be ≥55% after completion of neoadjuvant chemotherapy.3
ECOG PS=Eastern Cooperative Oncology Group performance status; HR=hormone receptor; IHC=immunohistochemistry; ISH=in situ hybridisation; LCIS=lobular carcinoma in situ; LVEF=left ventricular ejection fraction.
Patient demographics and baseline tumor characteristics1,2
§Five patients with a ypT1 tumor stage
had ypT1 disease without further subspecification.2
‖Other HER2-targeted agents were neratinib, dacomitinib, afatinib or lapatinib.2