A randomized phase II study of two different schedules of RAD001C in patients with recurrent/metastatic breast cancer

Abstract

3513 Background: RAD001C exerts antiproliferative and antiangiogenic effects by mTOR (mammalian target of rapamycin) inhibition. mTOR is critical in the transduction of proliferative signals mediated via the PI3K/Akt pathway. This signal transduction pathway is relevant to HER2 and ER signaling, and in PTEN mutated tumors, thus mTOR may be a central and relevant factor in breast cancer. Methods: Multi-center randomized phase II study assessing two oral schedules of RAD001C: Arm A (A)_10 mg daily, or Arm B (B)_70 mg weekly, assessed clinically each 4 weeks, imaged each 8 weeks. Eligibility: Patients (pts) with measurable metastatic breast cancer (MBC) who may have received adjuvant chemotherapy (CT), with up to one prior CT for advanced/recurrent disease. Stratification factors: 0 or 1 prior CT for MBC; presence/absence of visceral metastases. Primary endpoint: clinical/radiologic response and early progression (<8 wks). Two-stage accrual design with 15 evaluable pts in each arm in first phase. If =1 response and <10 early PD, add 15 pts. Arm B was discontinued after stage 1 as no responses were seen. A higher than expected occurrence of pneumonitis (Pn) occurred in both arms, higher in arm A. Results: Median age was 60yrs, 32 pts had prior CT, 20 pts had liver metastases. The most common drug related toxicities were fatigue, rash, anorexia, diarrhea, stomatitis, cough and pneumonitis; pulmonary effects appeared schedule related. (See results table below) Conclusions: Daily oral RAD001C has activity in MBC. The final results of this randomized Phase II trial will provide data to plan future breast cancer trials of RAD001C. [Table: see text] [Table: see text]