In a clinical trial, adding the CDK4/6 inhibitor Ibrance (palbociclib) to the hormonal treatment Faslodex (fulvestrant) delayed disease progression in postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer.
Adding Ibrance (palbociclib) to Faslodex (fulvestrant) as an initial therapy significantly improved the time from the start of treatment until disease worsened in postmenopausal patients with hormone receptor-positive, HER2-negative advanced breast cancer that is responsive to hormonal drugs.
Specifically, the drug combination boosted progression-free survival (PFS), meaning the proportion of patients living without disease progression, at a follow-up one year after the treatment was started. The study drug also improved the rate of partial and/or complete tumor response.
Palbociclib is a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. By blocking the activity of those two proteins, it prevents cancer cells from growing and dividing. Faslodex works by blocking the activity of estrogen.
The results came out of an international phase 2 clinical trial, GEICAM/2014-12, also known as the FLIPPER study, andwere presented at the European Society for Medical Oncology Virtual 2020 Congress by lead author Joan Albanell, a professor and head of medical oncology at Hospital del Mar in Barcelona, Spain.
The combination of Ibrance and Faslodex is a standard treatment for patients with hormone-driven, HER2-negative metastatic advanced breast cancer that has relapsed or progressed on previous hormone therapy. In this study, researchers tested the drugs in patients with metastatic disease known to be sensitive to hormone treatment.
Participants had newly diagnosed metastatic disease or cancer that had relapsed more than 12 months after the completion of five or more years of postsurgical hormone therapy.
The patients’ responses were also studied based on whether they had visceral versus non-visceral and recurrent versus new disease. The primary goal of the study was to measure PFS at one year.
From February 2016 to January 2019, 189 patients were enrolled in the study; 94 received Ibrance with Faslodex and 95 received placebo with Faslodex. Their average age was 64 years; 45.5% had newly diagnosed metastatic disease and 60.3% had visceral involvement.
The study met its goal: At an average follow-up of 28.6 months, one-year PFS rates were83.5% and 71.9% in the Ibrance versus the placebo groups, respectively. Average PFS was 31.8 months with Ibrance versus 22 months with placebo. Overall response rates, including all partial and/or complete tumor responses, were 68.3% in the Ibrance group compared with 42.2% in the placebo group.
The one-year PFS rate was significantly superior for the Ibrance versus the placebo group in those with visceral and newly diagnosed metastatic disease, but not in those with non-visceral or recurrent disease.
Data on the median length of life from the start of treatment were immature, and so couldn’t be reported.
The most frequent moderate to severe non-hematological side effects were diarrhea (3.2% vs. 2.1%) and fatigue (12.8% vs.5.3%) with Faslodex/Ibrance and Faslodex/placebo, respectively. Serious or severe hematological toxicities were neutropenia (64.9% vs. 0%), leukopenia (26.6% vs.0%) and lymphopenia (14.9% vs. 2.1%); those three conditions are white blood cell deficiencies. There were no reported cases of febrile neutropenia nor treatment-related deaths, Albanell reported. The toxicity profile was manageable with no unexpected side effects, he said.
“These data provide evidence for superiority of fulvestrant/palbociclib vs. fulvestrant/placebo in an advanced breast cancer population not represented in the pivotal PALOMA3 trial” that helped set the previous standard of care, the researchers concluded.