Abstract P1-14-01: Randomized controlled trial of toremifene 120 mg compared with exemestane 25 mg after prior non-steroidal aromatase inhibitor treatment in postmenopausal women with hormone receptor-positive metastatic breast cancer (Hi-FAIR ex study)
Authors: Yamamoto Y , Ishikawa T , Hozumi Y , Ikeda M , Kondo N , Yamashita H , Toyama T , Takashi C , Saji S , Yamamoto-Ibusuki M , Iwase H 
Published: August 2014

Abstract
(Background) After the failure of a non-steroidal aromatase inhibitor (nsAI) for postmenopausal patients with metastatic breast cancer (mBC), it is uncertain which of endocrine therapy is the most appropriate.
(Methods) A randomized, open-label, multicenter phase II study was conducted to compare the efficacy and safety of daily toremifene 120 mg (TOR120), a selective estrogen receptor modulator, with exemestane 25 mg (EXE), a steroidal aromatase inhibitor. After disease progressed with assigned drug, the patients were subsequently treated with the other drug if patients were suitable for continuation with endocrine treatment. The primary endpoint was clinical benefit rate (CBR). The secondary end points were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), toxicity and antitumor effect of subsequent endocrine treatment. To prove a probability of 90% that TOR120 was superior to EXE, 41 patients were required for each group. To account for dropouts and protocol violation, we planned to recruit 90 patients (45 in each group).
(Results) Initially, a total of 91women was registered in the study and randomly assigned to either TOR120 (n = 46) or EXE (n = 45) from October 2008 to November 2011. Three of the 46 patients in the TOR120 arm were not received treatment, 2 patients having withdrawn from the trial by their preference and one having been dropped due to administration of another SERM. When analyzed after a median observation period of 16.9 months, the intention-to-treat analysis showed that there was no statistical difference between TOR120 (n = 46) and EXE (n = 45) in terms of CBR (41.3% vs. 26.7%, p = 0.14), ORR (10.8% vs. 2.2%, p = 0.083), and OS (Hazard ratio (HR) 0.60, p = 0.22). The PFS of TOR120 was longer than that of EXE, the difference being statistically significant (HR 0.61, p = 0.045). Both treatments were well-tolerated with no severe adverse events, although the treatment of 3 of 43 women with TOR120 was stopped after a few days because of nausea, general fatigue, hot flash and night sweating. Twenty-four patients received subsequent TOR120 after failure of initial EXE treatment. Of these patients, ORR and CBR were 4.2% (1/24) and 33.3% (8/24), respectively. In 23 patients who received EXE after TOR120, ORR and CBR were 17.4% (4/23) and 30.4% (7/23), respectively.
(Conclusion) TOR120, as a subsequent endocrine therapy for mBC patients who failed non-steroidal AI treatment, could be equal to or potentially be more beneficial than EXE. In addition, about one third of patients who progress on either TOR120 or EXE could obtain clinical benefit from subsequent EXE or TOR120.
Trial registration number: UMIN000001841.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-14-01.