Table 1.

Summary of the study design, adverse events, and clinical outcomes from the 2 Z-endoxifen phase 1 clinical trials

Parameters	Goetz et al study, 2017 (49)	Takebe et al study, 2021 (50)
Patient enrollment details	Patients with metastatic or locally recurrent hormone receptor positive breast cancer.	Patients with hormone receptor positive solid breast tumors, desmoid tumors, or gynecologic tumors.
Prior treatment information	Progressed while receiving tamoxifen (if premenopausal) or an AI (if postmenopausal) in either the metastatic or adjuvant setting.	Progressed while receiving at least 1 prior chemotherapy regimen with or without at least 1 hormonal regimen in the metastatic setting. For HER2+ metastatic breast cancer, progressed on at least 1 prior HER2-directed regimen.
Limitations on prior therapy	None. Unlimited prior endocrine therapy regimens were allowed.	None.
Z-endoxifen dosages evaluated	20, 40, 60, 80, 100, 120 and 160 mg/d.	20, 40, 60, 100, 140, 200, 280 and 360 mg/d.
MTD	MTD not determined.	MTD not determined.
AE	Mostly grade 2 AE. Grade 4 hypertriglyceridemia noted at 60 mg/dose. No major AE reported at the highest dose (160 mg/d).	Most frequent AE were grades 2 and 3 lymphopenia and anemia. Grade 4 colonic perforation reported at the highest 360-mg dose.
Clinical benefit	Among the 25 patients with measurable disease, the overall response rate was 12.0% (95% CI, 2.6-31.2). Clinical benefit (stable disease ≥ 6 months) was observed in 19% of patients (3 of 16) who experienced progression during tamoxifen and 32% (7 of 22) who had no prior tamoxifen treatment or did not experience progression with adjuvant tamoxifen.	Breast cancer: 1/9 patients (11%) showed partial response; 3/9 patients (33%) experienced stable disease for ≥ 6 months. Desmoid tumors: 1/4 patients (25%) showed partial response; 2/4 patients (50%) experienced disease stabilization. Gynecologic tumors: 1/20 patients (5%) showed partial response; 3/20 patients (15%) experience disease stabilization of ≥ 6 cycles.

Abbreviations: AE, adverse event; AI, aromatase inhibitor; HER2, human epidermal growth factor 2 receptor; MTD, maximum tolerated dose.