The data presented at the 2020 ESMO Virtual Congress also discovered that the doublet regimen led to improvements in median PFS, objective response rate (ORR), and clinical benefit rate (CBR) compared with fulvestrant alone and demonstrated a manageable toxicity profile. FLIPPER is an ongoing randomized, double-blind, parallel-group, multicenter, international trial. The trial enrolled women who were postmenopausal; had HR-positive, HER2-negative metastatic breast cancer; endocrine-sensitive disease, as defined by relapse after adjuvant endocrine therapy of at least 5 years and a disease-free interval of more than 12 months, or de novo metastatic disease; an ECOG performance status of 0 to 2; and no prior therapy for metastatic disease.
The trial consisted of 189 patients who were randomized to either the experimental arm of fulvestrant and palbociclib (n = 94) or the control arm of fulvestrant and placebo (n = 95). Patients were categorized by visceral versus nonvisceral metastases and metastatic de novo presentation versus recurrent presentation at study entry. The primary endpoint was PFS rate at 1 year evaluated using RECIST v1.1 criterion. Secondary endpoints included median PFS, ORR, CBR, rate of overall survival at 1 and 2 years, safety and tolerability, and health-related quality of life. Researchers also evaluated data to identify promising biomarkers of response, monitoring, or resistance. At baseline, the average patient age was 64 years, visceral disease versus nonvisceral disease was present in about 60% versus 40% of patients, respectively, and the percentages of those with de novo versus recurrent disease were comparable.
The 1-year PFS rate was considered to meaningfully improve with the addition of palbociclib: 83.5% and 71.9% for those treated with palbociclib and placebo, respectively, with a hazard ratio (HR) of 0.55 (95% CI, 0.36-0.83; P =.064), which met the prespecified criteria for significance of a HR of 0.6 or lower. With regard to secondary study endpoints, average PFS was 31.8 months versus 22 months, with an HR that was adjusted according to stratification factors of 0.52 (95% CI, 0.39-0.68; P =.002). Researchers also noted that an exploratory investigation, 1-year PFS was assessed separately in those with and without visceral disease and those with de novo versus recurrent disease. The findings were substantial only for the subgroups with visceral disease and de novo disease.
In the overall study population, ORR and CBR were also considerably enhanced with the addition of palbociclib. Treatment-related adverse events (AEs) were detected in 89.4% of patients who received fulvestrant and palbociclib compared with 62.1% in those who received fulvestrant alone. An estimated 15% of patients in the investigational arm stopped palbociclib and 4.3% discontinued all study drugs, whereas 4.2% in the control arm discontinued treatment.
Serious AEs were reported in 26.6% of patients in the combination arm versus 20.0% in the monotherapy arm. Two on-study treatment deaths were reported in the fulvestrant and palbociclib arms, but neither was considered the result of treatment. In the investigational arm, the most common treatment-related hematological AEs were neutropenia in 68.1%, leukopenia in 26.6%, lymphopenia in 14.9%, and anemia in 3.2%, all of which were grade 3/4. No cases of febrile neutropenia were observed. The most common nonhematologic treatment-related AEs were fatigue (12.8%), diarrhea (3.2%), constipation (3.2%), and alanine aminotransferase increase (3.2%), which were all grades 2 through 4.
At the conclusion of the presentation, Joan Albanell, MD, head of medical oncology at Hospital del Mar, Barcelona, Spain, stated, “These data provide evidence for the superiority of fulvestrant plus palbociclib vs fulvestrant plus placebo in the first-line treatment of endocrine-sensitive hormone receptor-positive, HER2-negative metastatic breast cancer.”
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