Lucitanib may benefit selected patients with metastatic breast cancer

The VEGFR1-3, FGFR1-3 and PDGFRα/β inhibitor lucitanib shows modest antitumour activity and significant hypertension-related toxicity in patients with HR-positive, HER2-negative metastatic breast cancer (MBC), according to data from the phase II FINESSE study. Interestingly, the drug appears to confer greater benefits to patients with high FGFR1 expression.

FINESSE included three cohorts of patients with HR+/HER2− MBC who received oral lucitanib: FGFR1 amplified (cohort 1, n=32), FGFR1 nonamplified and 11q13 amplified (cohort 2, n=18), and FGFR1 and 11q13 nonamplified (cohort 3, n=26).  All patients had Eastern Cooperative Oncology Group Performance Status ≤2 and underwent ≥1 line of anticancer therapy but ≤2 lines of chemotherapy.

Researchers measured overall response rates (ORR) as the primary study endpoint. They used fluorescent in situ hybridization and droplet digital PCR to determine FGFR1 copy-number variation (CNV), as well as immunohistochemistry to evaluate FGFR1 expression.

The primary endpoint was met in cohort 1 only, with an ORR of 19 percent (95 percent confidence interval [CI], 9–35), but not in the other two cohorts. The respective ORRs in cohorts 2 and 3 were 0 percent (95 percent CI, 0–18) and 15 percent (95 percent CI, 6–34).

Commonly reported adverse events included hypertension (87 percent), hypothyroidism (45 percent), nausea (33 percent) and proteinuria (32 percent).

Exploratory biomarker analyses revealed higher ORR in the subgroup of patients with higher FGFR1 amplification (≥4 CNV) than in those without high amplification (22 percent vs 9 percent). The corresponding ORR in patients with FGFR1-high tumours (H-score ≥ vs <50) was 25 percent as opposed to 8 percent in those with FGFR1-low disease.