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

Rina Hui, Alex Pearson, Javier Cortes, Christine Campbell, Camille Poirot, Hatem A. Azim, Debora Fumagalli, Matteo Lambertini, Fergus Daly, Amal Arahmani, José Perez-Garcia, Philippe Aftimos, Philippe L. Bedard, Laura Xuereb, Elsemieke D. Scheepers, Malou Vicente, Theodora Goulioti, Sibylle Loibl, Sherene Loi, Marie Jeanne PierratNicholas C. Turner, Fabrice Andre, Giuseppe Curigliano

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)354-363
Number of pages10
JournalClinical Cancer Research
Volume26
Issue number2
DOIs
Publication statusPublished - Jan 15 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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