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

Purpose: The FGFRI gene is amplified in 14% of patients with HR+/HER2(-) breast cancer. Efficacy and safety of lucitanib, an inhibitor of VEGER 1-3, FGFRI-3, and PDGER alpha/beta, were assessed. Patients and Methods: Patients with HR+/HER2(-) metastatic breast cancer (MSC) received oral lucitanib in three centrally confirmed cohorts: (i) FGFR1 amplified, (ii) FGFRI nonamplified, 11q13 amplified, and (in) 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. FGFR 1 copy-number variation (CNV) was determined by FISH and droplet digital PCR, whereas EGER]. 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 ((,I), 9%-35%1, but not in cohorts 2 and 3 with ORR of0% (95% Cl, 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 FGLI(1 amplification (>= 4 (N V) 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 HR+/HER2(-) MEG. Although based on small sample sizes, exploratory biomarker analyses suggested that patients with high FGFRI amplification or expression might derive greater benefit.