Findings from a real-world, retrospective study conducted in Europe showed that outcomes for patients with advanced hormone receptor (HR)–positive/HER2-negative advanced breast cancer treated with first-line palbociclib (Ibrance) plus endocrine therapy (ET) support the use of this regimen as a frontline treatment option.1
Data published in Breast Cancer Research and Treatment demonstrated that evaluable patients treated in the United Kingdom (UK; n = 481) experienced an overall response rate (ORR) of 34.9% and a clinical benefit rate (CBR) of 80.7%. In patients from Spain (n = 251), the ORR and CBR were 43.8% and 86.1%, respectively. The respective ORR and CBR were 16.9% and 79.0% in patients from Germany (n = 124).
In the UK cohort, the median progression-free survival (PFS) and overall survival (OS) were 33.9 months (95% CI, 28.1-41.1) and 51.3 months (95% CI, 46.6-not evaluable [NE]), respectively. The median PFS was 28.1 months (95% CI, 24.6-35.1) in patients from Spain, who also experienced a median OS that was NE (95% CI, 47.5-NE). In the German cohort, the median PFS was 48.1 months (95% CI, 34.1-NE), and the median OS was 65.2 months (95% CI, 65.2-NE).
In the United States, palbociclib plus aromatase inhibitor is approved by the FDA as initial endocrine-based therapy for patients with HR-positive/HER2-negative advanced or metastatic breast cancer, based on data from the phase 3 PALOMA-2 trial (NCT01740427).2 Findings supporting the approval showed that patients who received palbociclib plus letrozole (n = 444) experienced an ORR of 55.3% (95% CI, 49.9%-60.7%), a median PFS of 24.8 months (95% CI, 22.1-NE), and a median OS of 53.8 months (95% CI, 49.8-59.2).
“This [retrospective] study adds to a growing body of real-world evidence supporting the clinical effectiveness of palbociclib and other CDK4/6 inhibitor combination therapies for [patients] with HR-positive/HER2-negative advanced breast cancer,” lead study author Olga Oikonomidou, BSc, MSc, MRes, MD, PhD, FRCP, and colleagues wrote in a publication of the data.1
Oikonomidou is a consultant medical oncologist, a senior clinical lecturer in Breast Cancer Medicine, and leader of the Breast Cancer Translational Research Group at the University of Edinburgh in Scotland.
“It is important to supplement findings from randomized clinical trials with real-world evidence from heterogeneous populations of patients in routine clinical practice who may be ineligible or underrepresented in clinical trials,” Oikonomidou and colleagues added.
How Real-World Palbociclib Data Were Gathered
To conduct the retrospective study, investigators identified patients from 52 treatment centers across the UK, Spain, and Germany. The study included patients at least 18 years of age with histologically or cytologically confirmed HR-positive/HER2-negative unresectable, advanced, or metastatic breast cancer who started first-line treatment with palbociclib plus an AI during the study index period from September 1, 2016, to July 31, 2020.
Investigators excluded patients who participated in a clinical trial evaluating a treatment for advanced, irrespective if participation occurred before or after first-line palbociclib. Patients were also excluded if they received prior treatment with any CDK4/6 inhibitor in the early-stage setting or received any CDK4/6 inhibitor–based regimen after first-line palbociclib.
The median age at diagnosis was 63.4 years (standard deviation [SD], 12.2) in the UK cohort, 61.9 years (SD, 12.8) in the Spain cohort, and 66.6 years (SD, 12.8) in the Germany cohort. Most patients were female (UK, 100%; Spain, 98.8%; Germany, 99.2%) and White (75.9%; 92.8%; 87.1%). The median duration of follow-up was 33.7 months in the UK group, 32.7 months in the Spain group, and 32.6 months in the Germany group.
The majority of patients in the UK cohort (62.0%) and Spain cohort (55.0%) were initially diagnosed with early-stage breast cancer, whereas most patients in the Germany cohort had de novo advanced disease (49.2%). Most patients in all 3 groups had a disease-free interval of more than 12 months (UK, 59.1%; Spain, 68.8%; Germany, 52.5%) and had 1 distant metastatic site (43.2%; 52.5%; 52.5%).
Across the 3 cohorts, patients had approximately 2 comorbidities at baseline, with the most common comprising hypertension (22.9%-45.2%), diabetes without end-organ damage (5.6%-12.1%), and depression (8.1%-11.6%).
Study Limitations
Oikonomidou and colleagues explained that data provided for this study were from centers willing to participate, meaning they may not be generalizable to other sites in different countries. They also noted that the study lacked a comparator arm, and sample sizes were limited for all 3 countries.
Additionally, since the study did not include patients who received subsequent CDK4/6 inhibitor–based regimens in the second or third line of therapy, study authors explained that these results may not be representative of this full patient population.
References
- Oikonomidou O, Beresford MJ, Galve-Calvo E, et al. Real-world clinical outcomes associated with first-line palbociclib and aromatase inhibitor therapy among patients with HR+/HER2- advanced breast cancer in Europe. Breast Cancer Res Treat. Published online August 6, 2025. doi:10.1007/s10549-025-07707-5
- Ibrance. Prescribing information. Updated April 2025. Accessed August 12, 2025. https://labeling.pfizer.com/ShowLabeling.aspx?id=2191#section-12
