Radical Trial: A Phase Lb/Iia Study To Assess The Safety And Efficacy Of Azd4547 In Combination With Either Anastrozole Or Letrozole In Er Positive Breast Cancer Patients Progressing On These Aromatase Inhibitors (Ais).

1059Background: Patients with metastatic ER positive breast cancer invariably experience disease progression whilst taking AIs. Fibroblast growth factor receptor inhibitors (FGFRI) such as AZD4547 can reverse endocrine resistance in breast cancer cells. Consequently, we designed the RADICAL trial to test the safety and efficacy of AZD4547 combined with letrozole (L) or anastrozole (A). Methods: Patients with prior disease progression on either AI were initially recruited to a Phase Ib study which showed that L 2.5mg or A 1mg daily continuously could be safely combined with AZD4547 80mg twice daily on a 1wk on/1 wk off schedule. Pharmacokinetic data showed no significant interactions. Subsequently, 52 patients progressing on these AIs were recruited, either continuing, or, if other therapies had subsequently been given, restarting their prior AI together with AZD4547. Primary endpoint was change in tumour size (RECIST v 1.1) at 12 weeks compared to baseline. Results: Enrolled patients had previously receiv...