Journal Article

A phase Ib dose allocation study of oral administration of lucitanib given in combination with fulvestrant in patients with estrogen receptor-positive and FGFR1-amplified or non-amplified metastatic breast cancer

Penault-Llorca, F, Dubois, F, Pallis, A, Poirot, C, Pierrat, M J, Campone, M, Lockhart, B, Guigal-Stephan, N, Xuereb, L, Bossard, C J, Andre, F, Bachelot, T, Agrapart, V

2019

Overview

PurposeThe primary objective of this multicentric dose allocation and dose expansion study was to determine the MTD and the DLTs of the lucitanib (a tyrosine kinase inhibitor of the FGFR/VEGFR/PDFGR pathways)/fulvestrant combination.MethodsPostmenopausal women with ER+/HER2− mBC, who have relapsed during or after treatment with fulvestrant, were eligible. The study had a dose allocation part to assess the tolerability of the combination followed by a dose expansion part.ResultsEighteen patients with ER+, mBC were enrolled; median age was 66 years, 50% had a PS: 0 and all had received previous endocrine treatment. The study was prematurely terminated after 18 patients (15 in part 1 and 3 in part 2) based on preclinical experiments that failed to confirm the hypothesis that addition of lucitanib would reverse sensitivity to endocrine treatments. Based on data of global lucitanib development, it was decided to stop the dose allocation at 12.5 mg and to start the dose expansion part at 10 mg/day. The most common grade ≥ 3 toxicities (> 10% of patients) were hypertension (78%) and asthenia (22%). All patients required at ≥ 1 interruption, 13 patients (72%) required ≥ 1 dose reduction. Three patients (72%) withdrew from the study for AEs (at 10 mg). Three patients achieved a confirmed PR (10 mg n = 1; 12.5 mg n = 2).ConclusionAlthough the combination is feasible it requires close monitoring of the patients for the management of adverse events. Further investigation is required to better understand the potential role of FGFR inhibition in reversing resistance to endocrine treatment.

• Publisher: Springer Nature B.V
• Subject: Asthenia / Breast cancer / Enzyme inhibitors / ErbB-2 protein / Estrogen receptors / Fibroblast growth factor receptor 1 / Fibroblast growth factor receptors / Fulvestrant / Metastases / Oral administration / Patients / Post-menopause / Protein-tyrosine kinase / Vascular endothelial growth factor receptors