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.

Lucitanib for the treatment of HRþ/HER2- Metastatic breast cancer : Results from the multicohort phase II FINESSE study / R. Hui, A. Pearson, J. Cortes, C. Campbell, C. Poirot, H.A. Azim, D. Fumagalli, M. Lambertini, F. Daly, A. Arahmani, J. Perez-Garcia, P. Aftimos, P.L. Bedard, L. Xuereb, E.D. Scheepers, M. Vicente, T. Goulioti, S. Loibl, S. Loi, M.-. Pierrat, N.C. Turner, F. Andre, G. Curigliano. - In: CLINICAL CANCER RESEARCH. - ISSN 1078-0432. - 26:2(2020), pp. 354-363. [10.1158/1078-0432.CCR-19-1164]

Lucitanib for the treatment of HRþ/HER2- Metastatic breast cancer : Results from the multicohort phase II FINESSE study

G. Curigliano
Conceptualization
2020

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.
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
Settore MED/06 - Oncologia Medica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/824444
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