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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
- Source :
- Cancer Chemotherapy and Pharmacology, Cancer Chemotherapy and Pharmacology, Springer Verlag, 2019, 83 (4), pp.743-753. ⟨10.1007/s00280-018-03765-3⟩, Cancer Chemotherapy and Pharmacology, 2019, 83 (4), pp.743-753. ⟨10.1007/s00280-018-03765-3⟩
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- 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. 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. 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). 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.
- Subjects :
- 0301 basic medicine
Oncology
Cancer Research
Administration, Oral
Estrogen receptor
Toxicology
Tyrosine-kinase inhibitor
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
Medicine
Pharmacology (medical)
Neoplasm Metastasis
Fulvestrant
Hormone receptor positive
Middle Aged
Metastatic breast cancer
3. Good health
Postmenopause
Receptors, Estrogen
Tolerability
030220 oncology & carcinogenesis
embryonic structures
VEGF pathway lucitanib
Quinolines
Female
medicine.drug
medicine.medical_specialty
Maximum Tolerated Dose
medicine.drug_class
FGFR Inhibition
[SDV.CAN]Life Sciences [q-bio]/Cancer
Breast Neoplasms
FGF pathway
Naphthalenes
03 medical and health sciences
Internal medicine
Humans
Endocrine system
Receptor, Fibroblast Growth Factor, Type 1
Adverse effect
Aged
Pharmacology
Dose-Response Relationship, Drug
business.industry
medicine.disease
030104 developmental biology
business
Subjects
Details
- ISSN :
- 14320843 and 03445704
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- Cancer Chemotherapy and Pharmacology
- Accession number :
- edsair.doi.dedup.....538177d9016132fe5f39143b6e44b3a8