The following article features coverage from the European Society for Medical Oncology 2020 virtual meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

One-year progression-free survival (PFS) in the first-line treatment of hormone receptor-positive, HER2-negative metastatic breast cancer was significantly longer for those patients treated with fulvestrant plus the CDK4/6 inhibitor palbociclib compared with fulvestrant plus placebo, according to results of a phase 2 trial presented at the European Society of Medical Oncology (ESMO) Virtual Congress 2020.1

Previously reported results of the phase 3 PALOMA3 trial demonstrated superior efficacy for fulvestrant plus palbociclib compared with fulvestrant plus placebo for patients with hormone receptor-positive, HER2-negative metastatic breast cancer that had relapsed or progressed on endocrine therapy administered in the metastatic setting.2 Furthermore, this finding contributed to the US Food and Drug Administration (FDA) approval of this indication for palbociclib plus fulvestrant, which was limited to the use of this combination only following disease progression on prior endocrine therapy.3

Hence, a rationale for the design of the phase 2 FLIPPER study ( Identifier: NCT02690480) was to investigate the combination of palbociclib plus fulvestrant compared with placebo plus fulvestrant as first-line treatment for women with hormone receptor-positive, HER2-negative metastatic breast cancer.

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This was a double-blinded, placebo-controlled trial in which 189 postmenopausal women with hormone receptor-positive metastatic breast cancer that represented either de novo disease or had relapsed following at least 5 years of adjuvant therapy with a disease-free interval of at least 12 months were randomly assigned in a 1:1 ratio to the 2 treatment arms. These patients had not received prior treatment for metastatic disease.

Patients were stratified according to whether metastatic disease was visceral vs not, as well as whether metastatic disease represented recurrent disease following treatment with adjuvant therapy or was classified as de novo disease.

The primary study endpoint was the rate of 1-year PFS, with secondary study endpoints including median PFS, overall response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and safety.

At baseline, the median patient age was 64 years, visceral disease vs not was present in approximately 60% vs 40%, respectively, and the percentages of those with de novo vs recurrent disease were similar.

The 1-year PFS rate was considered to significantly improved with the addition of palbociclib: it was 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 criterion for significance of a HR of 0.6 or lower.

When considering secondary study endpoints, median PFS was 31.8 months vs 22 months, with a HR that was adjusted according to stratification factors of 0.52 (95% CI, 0.39-0.68; P =.002).

In an exploratory analysis, 1-year PFS was evaluated separately in those with and without visceral disease, and those with de novo versus recurrent disease. Findings were significant only for the subgroups with visceral disease and de novo disease.

“As you know, in these exploratory analyses, the results are hypothesis-generating and have to be evaluated as such,” noted Joan Albanell, MD, head of medical oncology at Hospital del Mar, Barcelona, Spain, who was the presenting author.

In the overall study population, ORR and CBR were also significantly improved with addition of palbociclib.

Regarding safety, the frequencies of serious adverse events (AEs) were 26.6% and 20.0% for patients treated with palbociclib and placebo, respectively. However, frequencies of grade 3/4 hematologic AES, such as neutropenia, were much higher in the palbociclib arm (68.1%) compared with the placebo arm (0%). Similarly, the frequencies of leukopenia and lymphopenia were considerably higher for those receiving palbociclib vs placebo.

In his closing remarks, Dr Albanell stated that “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.”

Disclosures: Research funding for this study was provided by AstraZeneca and the GEICAM Spanish Breast Cancer Group was the legal entity responsible for the study. For a full list of disclosures, please refer to the study abstract.

Read more of Cancer Therapy Advisor‘s coverage of the ESMO Virtual Congress 2020 by visiting the conference page.


  1. Albanell J, Martinez MT, 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). Presented at: European Society of Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. Abstract LBA19.
  2. Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016;17:425-439. doi: 10.1016/S1470-2045(15)00613-0
  3. Palbociclib (Ibrance®) [package insert]. New York, NY: Pfizer, Inc.; 2019.