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

Abstract

The <i>FGFR1</i> gene is amplified in 14% of patients with HR <b>⁺</b> /HER2 <b>^-</b> breast cancer. Efficacy and safety of lucitanib, an inhibitor of VEGFR1-3, FGFR1-3, and PDGFRα/β, were assessed. Patients with HR <b>⁺</b> /HER2 <b>^-</b> metastatic breast cancer (MBC) received oral lucitanib in three centrally confirmed cohorts: (i) <i>FGFR1</i> amplified, (ii) <i>FGFR1</i> nonamplified, 11q13 amplified, and (iii) <i>FGFR1</i> 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. <i>FGFR1</i> 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 <i>FGFR1</i> 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 <b>⁺</b> /HER2 <b>^-</b> MBC. Although based on small sample sizes, exploratory biomarker analyses suggested that patients with high <i>FGFR1</i> amplification or expression might derive greater benefit.