Preliminary Results from a Phase 2 Trial of Fulvestrant/Palbociclib as First-Line Therapy in Postmenopausal Women with Hormone Receptor–Positive, HER2-Negative Endocrine-Sensitive Advanced Breast Cancer

Adding palbociclib to fulvestrant as first-line therapy improves 1-year progression-free survival in postmenopausal women with hormone receptor–positive, HER2-negative, endocrine-sensitive, advanced breast cancer.

Joan Albanell, MD, Director, Medical Oncology, Hospital del Mar, Barcelona, Spain, provided insight on the role of palbociclib combined with fulvestrant on improving outcomes of endocrine-sensitive advanced breast cancer. The FLIPPER clinical trial was designed to look at postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer with de novo metastatic disease or relapsing condition after >12 months of completing ≥5 years of adjuvant endocrine therapy.

In this double-blind phase 2 study, 189 patients were randomized to receive in a 1:1 ratio fulvestrant 500 mg plus palbociclib or fulvestrant plus placebo. Visceral versus nonvisceral and recurrent versus de novo metastatic disease were used as stratification criteria. The primary outcome of the study was progression-free survival at 1 year using the investigator’s assessment by Response Evaluation Criteria in Solid Tumors version 1.1.

The 1-year progression-free rate of the patients who received the palbociclib plus fulvestrant combination was 83.5%, which was significantly higher than the 71.9% rate for women who received placebo with fulvestrant (hazard ratio [HR], 0.55; 80% confidence interval [CI], 0.36-0.83; P = .064). The median progression-free survival of the palbociclib arm was also significantly longer than that of the placebo arm: 31.8 months for the palbociclib plus fulvestrant group versus 22.0 months for the fulvestrant plus placebo group (HR, 0.52; 95% CI, 0.34-0.78; P = .002).

Stratification by the stage and site of disease revealed that there was significant benefit to progression-free survival by adding palbociclib to fulvestrant. Furthermore, the overall response rate (ORR) for fulvestrant plus placebo was 42.2% compared with 68.3% for the palbociclib plus fulvestrant arm (P = .004). Toxicities that were most frequently reported (grade 2/4) were fatigue (12.8% vs 5.3%) and diarrhea (3.2% vs 2.1%) and with palbociclib plus fulvestrant and fulvestrant plus placebo, respectively. Hematologic toxicities (grade 3/4) were neutropenia (64.9% vs 0%), lymphopenia (14.9% vs 2.1%), and leukopenia (26.6% vs 0%) in the palbociclib plus fulvestrant arm and the fulvestrant plus placebo arm. There were no reports of treatment-related deaths or febrile neutropenia. At the time of the presentation, overall survival data were not fully developed.

The investigators concluded that the combination of palbociclib plus fulvestrant significantly improved 1-year progression-free survival, also improving median progression-free survival and ORR. This is particularly important because it suggests superiority of palbociclib plus fulvestrant compared with fulvestrant plus placebo when utilized in a patient population of women with advanced breast cancer who were not included in the PALOMA3 trial.

Source: Albanell J, Martinez MTM, Ramos M, et al. GEICAM/2014-12 (FLIPPER) study: first analysis from a randomized phase II trial of fulvestrant (F)/palbociclib (P) versus (vs) F/placebo (PL) as first-line therapy in postmenopausal women with HR (hormone receptor)+/HER2– endocrine sensitive advanced breast cancer (ABC). Ann Oncol. 2020;31(4_suppl). Abstract LBA19.

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