LBA19 - 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)

Background

The role of P combined with F in improving outcomes of endocrine sensitive ABC patients (pts) in the first-line setting deserved clinical testing. To study this, postmenopausal HR+/HER2– ABC with de novo metastatic disease or relapsing after >12 months of completing ≥5 years of adjuvant endocrine therapy were included in FLIPPER study.

Methods

In this double-blind phase II study, pts were randomly assigned in 1:1 ratio to F 500mg/P vs. F/PL. Stratification criteria were: visceral vs. non-visceral and recurrent vs. de novo metastatic disease. The primary objective was progression-free survival (PFS) at 1 year (investigator’s assessment by RECIST 1.1). With a sample size of 190 pts and a two-sided alpha of 0.2, the analysis has 80% power to detect a difference between both treatment groups, assuming PFS proportions of 0.545 and 0.695 for F/PL and F/P, respectively (constant HR of 0.6).

Results

From Feb’2016 to Jan’2019, 189 pts were randomised (94 F/P, 95 F/PL). Median age was 64 years, 45.5% of pts had de novo metastatic disease, 60.3% visceral involvement. The study met the pre-specified primary endpoint: PFS rates at 1-year were 83.5% and 71.9% in F/P and F/PL groups, respectively (HR 0.55; 80% CI 0.36-0.83, p=0.064). Median PFS was 31.8 mo (F/P) vs. 22.0 mo (F/PL) (HR 0.52; 95% CI 0.34-0.78; p=0.002). Overall response rates were 68.3% (F/P) vs. 42.2% (F/PL) (p=0.004). The most frequent G2/4 non-haematological toxicities were diarrhoea (3.2% vs. 2.1%) and fatigue (12.8% vs. 5.3%) with F/P and F/PL, respectively. G3/4 haematological toxicities were neutropenia (64.9% vs. 0%), leukopenia (26.6% vs. 0%) and lymphopenia (14.9% vs. 2.1%). There were no reported cases of febrile neutropenia nor treatment related deaths. OS data are immature.

Conclusions

P/F significantly improved 1-year PFS rate compared to F/PL in pts with HR+/HER2- endocrine sensitive ABC. P/F also improved median PFS and ORR. These data provide evidence for superiority of F/P vs. F/PL in an ABC population not represented in the pivotal PALOMA3 trial.

Clinical trial identification

NCT02690480.

Editorial acknowledgement

Legal entity responsible for the study

GEICAM Spanish Breast Cancer Group.

Funding

AstraZeneca.

Disclosure

J. Albanell: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly. M. Ramos: Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Pfizer. M. O' Connor: Research grant/Funding (institution): HRB grant to UHW Oncology; Full/Part-time employment: University Hospital Waterford. L. De la Cruz-Merino: Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck; Research grant/Funding (institution): Celgene; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: MSD. A. Santaballa Bertran: Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: GSK; Advisory/Consultancy: Clovis; Advisory/Consultancy: Roche; Advisory/Consultancy: Pierre Fabre. F. Moreno: Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self): MSD; Honoraria (self): AstraZeneca. I. Fernández Pérez: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: Tesaro- MSD. M. Margeli Vila: Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novartis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Kern-Pharma. F. Rojo Todo: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Archer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre. All other authors have declared no conflicts of interest.