Futibatinib-fulvestrant combination active in FGFR1-amplified advanced breast cancer
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SAN ANTONIO — Futibatinib plus fulvestrant exhibited antitumor activity among certain patients with locally advanced or metastatic breast cancer with fibroblast growth factor receptor 1 amplification, according to study results.
Adults with advanced hormone receptor-positive, HER2-negative disease with FGFR1 amplification who progressed on cyclin-dependent kinase 4/6 inhibitors achieved better response and longer PFS compared with historical results of fulvestrant alone in this setting, findings presented at San Antonio Breast Cancer Symposium showed.
FGFR1 gene amplification and overexpression is reported in approximately 10% of invasive breast cancers. It is associated with poor prognosis among patients with hormone receptor-positive, HER2-negative breast cancer, according to study background.
Futibatinib (Lytgobi, Taiho Oncology) — an irreversible covalent inhibitor of FGFR1-4 — is approved for treatment of intrahepatic cholangiocarcinoma.
Senthil Damodaran, MD, PhD, associate professor in the department of breast medical oncology at The University of Texas MD Anderson Cancer Center, and colleagues conducted the phase 2 FOENIX-MBC2 study to assess futibatinib alone or in combination with fulvestrant for patients with metastatic breast cancer.
At SABCS, Damodaran presented results from a cohort of patients with hormone receptor-positive, HER2-negative breast cancer who harbored high-level FGFR1 gene amplification who received futibatinib plus fulvestrant.
All patients experienced disease progression after prior therapy for advanced or metastatic disease. They all had measurable disease and ECOG performance status of 0 or 1. None had received fulvestrant; however, they had received one or two endocrine-containing therapies, up to one chemotherapy regimen and a CDK 4/6 inhibitor for advanced cancer unless they had been ineligible for such treatment.
Study protocol defined high-level FGFR1 gene a as FGFR1/centromere 8 ratio of at least 5, or FGFR1 copy number of at least 10 signals per cell.
Patients received 20 mg futibatinib orally once daily plus standard fulvestrant. Treatment continued until disease progression or unacceptable toxicity, or until patients met other discontinuation criteria.
Six-month PFS served as the primary endpoint. Secondary endpoints included PFS, objective response rate and safety.
The analysis included 22 women (median age, 58 years) who had received a median three prior lines of systemic anticancer therapy. All had received prior CDK 4/6 inhibitor therapy.
Ten patients (45.5%; 95% CI, 24.4-67.8) achieved 6-month PFS, with median PFS of 7.2 months (95% CI, 2.1-7.6).
Four patients (18.2%; 95% CI, 5.2-40.3) achieved confirmed partial response, with a median response duration of 6.3 months (range, 3.3-12.8).
All patients experienced at least one treatment-related adverse event, the most common of which included hyperphosphatemia (95.5%), alopecia (54.5%), constipation (45.5%) and dry mouth (40.9%).
Five patients (22.7%) experienced grade 3 treatment-related adverse events. No grade 4 or grade 5 events occurred, nor did any treatment-related serious adverse events occur.
Treatment-related adverse events led to treatment interruption for nine patients (40.9%), treatment reduction for 15 patients (68.2%), and treatment discontinuation for two patients (9.1%).
Researchers are performing additional analyses to identify biomarkers that may be predictive of treatment benefit.
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Damodaran S, et al. Abstract RF01-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2023; San Antonio.
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