Lucitanib for the treatment of HR+/ HER2- metastatic breast cancer: results from the multicohort phase II FINESSE study.

FGFR1 gene is amplified in 14% of HR⁺/ HER2^- breast cancer patients. Efficacy and safety of lucitanib, an inhibitor of VEGFR1-3, FGFR1-3 and PDGFRα/β, were assessed.

HR⁺/ HER2^- MBC patients received oral lucitanib in 3 centrally confirmed cohorts: 1) FGFR1 amplified, 2) FGFR1 non-amplified, 11q13 amplified, 3) FGFR1 and 11q13 non-amplified. Key inclusion criteria included ECOG PS <2, >1 line of anti-cancer therapy, but <2 lines of chemotherapy. Primary endpoint was ORR by RECIST1.1. Simon's 2-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) were determined by FISH and ddPCR, while FGFR1 expression by IHC.

76 patients (32/18/26 in cohorts 1/2/3) from nine countries were enrolled. The pre-specified primary endpoint was met in cohort 1 with ORR of 19% (95%CI:9-35%), but not in cohorts 2 and 3 with ORR of 0% (0-18%) and 15% (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% versus 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 patients with high FGFR1 amplification or expression might derive greater benefit.