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

Abstract

Purpose: The FGFR1 gene is amplified in 14% of patients with HR þ /HER2 À breast cancer. Efficacy and safety of lucitanib, an inhibitor of VEGFR1-3, FGFR1-3, and PDGFRa/b, were assessed.Patients and Methods: Patients with HR þ /HER2 À 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 HR þ / HER2 À MBC. Although based on small sample sizes, exploratory biomarker analyses suggested that patients with high FGFR1 amplification or expression might derive greater benefit.

Occult metastatic thyroid cancer diagnosed during breast cancer axillary sentinel node biopsy

“…Lenvatinib, a multi-kinase inhibitor targeting VEGFR1-3, FGFR1-4, PDGFR, RET and KIT is an effective treatment for metastatic thyroid cancer and could be used if there is further metastatic spread or the thyroid cancer deposit fails to respond (13). Although preliminary clinical data suggested a possible role in targeting FGFR1 in some patients with hormone receptor positive, HER2 negative, advanced breast cancer, this type of targeted therapy is still in early clinical development and is not standard of care (14).…”

Resistance to cyclin-dependent kinase (CDK) 4/6 inhibitors confers cross-resistance to other CDK inhibitors but not to chemotherapeutic agents in breast cancer cells

“…However, their anti-tumor activity remains to be clarified. In addition, based on preclinical studies suggesting that activation mutations or amplification of the FGFR pathway cause acquired resistance to CDK4/6 inhibitors, the FGFR tyrosine kinase inhibitor lucitanib has been clinically tested in patients with advanced breast cancer [14].…”

Microfluidic Droplet Digital PCR Is a Powerful Tool for Detection of BRAF and TERT Mutations in Papillary Thyroid Carcinomas

“…It has to be noted that in contrast to NGS which can be a lengthy process, dPCR's turnaround time is less than 24 hours, that can be particularly helpful in the cases of aggressive malignancies where time is of the essence [56]. In addition, cost for dPCR is significantly lower than NGS.…”