Reference Detail

Ref Type

Journal Article

PMID

(31619444)

Authors

Hui R, Pearson A, Cortes J, Campbell C, Poirot C, Azim HA, Fumagalli D, Lambertini M, Daly F, Arahmani A, Perez-Garcia J, Aftimos P, Bedard PL, Xuereb L, Scheepers ED, Vicente M, Goulioti T, Loibl S, Loi S, Pierrat MJ, Turner NC, Andre F, Curigliano G

Title

Lucitanib for the Treatment of HR+/HER2- Metastatic Breast Cancer: Results from the Multicohort Phase II FINESSE Study.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research	26	2	2020 Jan 15	354-363	Clin Cancer Res

URL

Abstract Text

The FGFR1 gene is amplified in 14% of patients with HR + /HER2 - breast cancer. Efficacy and safety of lucitanib, an inhibitor of VEGFR1-3, FGFR1-3, and PDGFRα/β, were assessed.Patients with HR + /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.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.Lucitanib had modest antitumor activity and significant hypertension-related toxicity in patients with HR + /HER2 - MBC. Although based on small sample sizes, exploratory biomarker analyses suggested that patients with high FGFR1 amplification or expression might derive greater benefit.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
Lucitanib	Lucitanib	6	5

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Lucitanib		E-3810\|AL3810	DDR1 Inhibitor 10 DDR2 inhibitor 7 FGFR1 Inhibitor 28 FGFR2 Inhibitor 23 PDGFR-alpha Inhibitor 9 VEGFR Inhibitor (Pan) 36	Lucitanib (E-3810) is a multi-tyrosine kinase receptor inhibitor of VEGFR 1-3, DDR2, PDGFRA, and FGFR1-2, that may inhibit tumor angiogenesis, prevent tumor cell proliferation, and induce tumor cell death (PMID: 27988457, PMID: 24696502, PMID: 31619444).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
FGFR1 over exp	Her2-receptor negative breast cancer	predicted - sensitive	Lucitanib	Phase II	Actionable	In a Phase II (FINESSE) trial, Lucitanib (E-3810) treatment resulted in improved objective response rate (25%, 5/20 vs 8%, 3/39) and median progression-free survival (158 vs 109 days) in patients with metastatic hormone receptor-positive, Erbb2 (Her2)-negative breast cancer with high Fgfr1 expression (H-score>=50) compared to those with low Fgfr1 expression (H-score<50) (PMID: 31619444; NCT02053636).	31619444
FGFR1 amp	Her2-receptor negative breast cancer	predicted - sensitive	Lucitanib	Phase II	Actionable	In a Phase II (FINESSE) trial, Lucitanib (E-3810) treatment resulted in an objective response rate (ORR) of 19% (6/32) and a clinical benefit rate of 41% (13/32) in patients with metastatic hormone receptor-positive, Erbb2 (Her2)-negative breast cancer harboring FGFR1 amplification, ORR was improved (22%, 5/23 vs 9%, 5/53) in patients with high level FGFR1 amplification (FGFR1/centromere ratio>=4) compared to those without (PMID: 31619444; NCT02053636).	31619444