Abstract P3-11-02: A randomized phase II trial of toremifene (120 mg) versus fulvestrant (500 mg) after prior non-steroidal aromatase inhibitor in postmenopausal women with hormone receptor-positive metastatic breast cancer (Hi-FAIR fx study)
Authors: Nishimura R , Yamamoto Y , Narui K , Kijima Y , Hozumi Y , Ikeda M , Takao S , Ohtani S , Iwase H 
Published: February 2018

Abstract
Background: After the failure of a non-steroidal aromatase inhibitor (nsAI) for postmenopausal patients with advanced/metastatic breast cancer (BC), it is unclear which of the various kinds of endocrine monotherapy is the most appropriate. In a previous report it was found that toremifene 120 mg (TOR 120), a selective estrogen receptor modulator (SREM), was superior to steroidal AI in terms of progression-free survival after ns-AI in the Hi-FAIR ex trial. A phase II randomized trial of TOR 120 versus fulvestrant 500 mg (FUL 500), a selective estrogen receptor down regulator (SERD), was also conducted to select the most promising endocrine monotherapy after ns-AI in advanced/metastatic BC(Study registry number: UMIN000010087).
Patients and Methods: Postmenopausal women (n=106) with advanced/metastatic hormone-receptor positive BC from October 2011 to September 2014 were enrolled in this study. Fifty-three of the patients were randomly assigned to the TOR 120 (120 mg daily p.) group and 53 of the patients were randomly assigned to the FUL 500 group. In the FUL 500 group they were administered 500 mg of fulvestrant intramuscularly (im) on day 0, then 500 mg im on days 14 and 28 and every 28 days thereafter). If treatment failure occurred in either of the randomly assigned groups the patients were then removed and treated accordingly. A full analysis set was targeted for all cases that received the protocol treatment even once (TOR 120 (n=53) and FUL 500 (n=52)). The primary end point was the clinical benefit rate (CBR). The secondary end points were the objective response rate (ORR), progression-free survival (PFS), time to chemotherapy (TTCT), overall survival (OS), toxicity, and CBR, ORR and PFS after crossover of non-assigned treatment.
Results: A median follow up period of 30 months revealed that the CBR of FUL 500 (57.7%) tended to be superior to the CBR of TOR 120 (45.3%), the odds ratio (OR) was 1.70 (95% CI 0.74–3.62), and the median PFS was 7.8 months in the FUL 500 group and 5.8 months in the TOR 120 group. Moreover the hazard ratio (HR) was 0.79 (95% CI 0.52–1.21). However, there was no difference between the two groups in terms of ORR (17.7% and 15.1%, respectively), TTCT (13.3 months vs. 17.7 months, HR = 0.94 (95%CI 0.57 – 1.53)), and OS (33.4 months vs. not reached HR 1.29; 95% CI 0.80–2.09). At the cross-over phase, 33 and 24 patients after failure of assigned treatment were treated with FUL 500 and TOR 120, respectively. The CBR and PFS of FUL 500 after TOR 120 was better than that of TOR 120 after FUL 500 (CBR; 42.4% vs. 20.8%, OR = 0.33, 95%CI 0.09 – 1.11, median PFS; 6.2 months vs. 3.4 months; HR = 1.95, 95%CI 1.08–3.51). No difference between the two groups was observed in PFS from randomization to the end of the crossover phase. Moreover, there were few severe adverse events in either of the two groups.
Conclusions: FUL 500 used as a subsequent endocrine therapy for advanced/metastatic BC patients who failed ns-AI could potentially be more effective than TOR 120. However, the efficacy of SERM after failure of FUL 500 may be limited.
Citation Format: Nishimura R, Yamamoto Y, Narui K, Kijima Y, Hozumi Y, Ikeda M, Takao S, Ohtani S, Iwase H. A randomized phase II trial of toremifene (120 mg) versus fulvestrant (500 mg) after prior non-steroidal aromatase inhibitor in postmenopausal women with hormone receptor-positive metastatic breast cancer (Hi-FAIR fx study) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-11-02.