M Campone1, T Bachelot2, F Penault-Llorca3, A Pallis4, V Agrapart4, M J Pierrat4, C Poirot4, F Dubois4, L Xuereb4, C J Bossard5, N Guigal-Stephan5, B Lockhart5, F Andre6. 1. Institut de Cancérologie de l'Ouest-Centre René Gauducheau, Saint-Herblain, France. mario.campone@ico.unicancer.fr. 2. Centre Léon Bérard Centre de Lutte Contre le Cancer (CLCC) de Lyon, Lyon, France. 3. Centre Jean Perrin, Clermont-Ferrand, France. 4. Institut de Recherches Internationales Servier, Suresnes, France. 5. Institut de Recherches Servier, Croissy-sur-Seine, France. 6. Institut Gustave Roussy, Villejuif, France.
Abstract
PURPOSE: The 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. METHODS: Postmenopausal 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. RESULTS: Eighteen 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). CONCLUSION: Although 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.
PURPOSE: The 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. METHODS: Postmenopausal 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. RESULTS: Eighteen 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). CONCLUSION: Although 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.
Authors: Miguel Quintela-Fandino; Juan V Apala; Diego Malon; Silvana Mouron; Javier Hornedo; Lucia Gonzalez-Cortijo; Ramon Colomer; Juan Guerra Journal: Breast Cancer Res Date: 2019-05-24 Impact factor: 6.466
Authors: Miguel Quintela-Fandino; Maria J Bueno; Silvana Mouron; Luis Manso; Eduardo Caleiras; Jose L Rodriguez-Peralto; Oscar M Rueda; Carlos Caldas; Ramon Colomer Journal: Breast Cancer Res Date: 2021-02-12 Impact factor: 6.466