Lucitanib for the treatment of HRþ/HER2- Metastatic breast cancer: Results from the multicohort phase II FINESSE study
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American Association for Cancer Research Inc.
Abstract
Purpose: The FGFR1 gene is amplified in 14% of patients with HRþ/HER2- breast cancer. Efficacy and safety of lucitanib, an inhibitor of VEGFR1-3, FGFR1-3, and PDGFRa/b, were assessed. Patients and Methods: Patients with HRþ/HER2- metastatic breast cancer (MBC) received oral lucitanib in three centrally confirmed cohorts: (i) FGFR1 amplified, (ii) FGFR1 nonamplified, 11q13 amplified, and (iii) FGFR1 and 11q13 nonamplified. Key inclusion criteria included Eastern Cooperative Oncology Group Performance Status ≤2, ≥1 line of anticancer therapy, but ≤2 lines of chemotherapy. Primary endpoint was overall response rates (ORR) by RECIST1.1. Simon's two-stage design was used: If ≥2 patients responded among 21 patients, 20 additional patients could be enrolled in each cohort. FGFR1 copy-number variation (CNV) was determined by FISH and droplet digital PCR, whereas FGFR1 expression was determined by IHC. Results: Seventy-six patients (32/18/26 in cohorts 1/2/3) from nine countries were enrolled. The prespecified primary endpoint was met in cohort 1 with ORR of 19% [95% confidence interval (CI), 9%–35%], but not in cohorts 2 and 3 with ORR of 0% (95% CI, 0%–18%) and 15% (95% CI, 6%–34%), respectively. Frequent adverse events included hypertension (87%), hypothyroidism (45%), nausea (33%), and proteinuria (32%). Exploratory biomarker analyses suggested higher ORR in patients with high FGFR1 amplification (≥4 CNV) than those without high amplification (22% vs. 9%). ORR in patients with FGFR1-high tumors (IHC, H-score ≥50) was 25% versus 8% in FGFR1-low cancers. Conclusions: Lucitanib had modest antitumor activity and significant hypertension-related toxicity in patients with HRþ/ HER2- MBC. Although based on small sample sizes, exploratory biomarker analyses suggested that patients with high FGFR1 amplification or expression might derive greater benefit. © 2020 American Association for Cancer Research.
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Adult, Aged, Biomarkers, tumor, Breast neoplasms, Estrogen receptor alpha, Female, Gene amplification, Humans, Middle aged, Molecular targeted therapy, Naphthalenes, Neoplasm metastasis, Patient safety, Protein kinase inhibitors, Quinolines, Receptor, erbb-2, Receptor, fibroblast growth factor, type 1, Receptors, progesterone, Treatment outcome, Biological marker, Fibroblast growth factor 23, Fibroblast growth factor receptor 1, Lucitanib, E-3810, Epidermal growth factor receptor 2, Erbb2 protein, human, Estrogen receptor alpha, human, Fgfr1 protein, human, Naphthalene derivative, Progesterone receptor, Protein kinase inhibitor, Quinoline derivative, Tumor marker, Abdominal pain, Antineoplastic activity, Article, Asthenia, Cancer chemotherapy, Cohort analysis, Controlled study, Copy number variation, Diarrhea, Droplet digital polymerase chain reaction, Drug dose reduction, Drug efficacy, Drug safety, Drug withdrawal, Fatigue, Fgfr1 gene, Fluorescence in situ hybridization, Gene expression, Headache, Human, Human cell, Human epidermal growth factor receptor 2 negative breast cancer, Human tissue, Hypertension, Hypothyroidism, Immunohistochemistry, Loss of appetite, Major clinical study, Metastatic breast cancer, Monotherapy, Multicenter study, Multiple cycle treatment, Myalgia, Nausea, Open study, Phase 2 clinical trial, Priority journal, Proteinuria, Response evaluation criteria in solid tumors, Thrombocytopenia, Treatment response, Vomiting, Breast tumor, Clinical trial, Genetics, Metabolism, Metastasis, Molecularly targeted therapy, Pathology