Real-World Evidence Supports Efficacy of Palbociclib Plus Letrozole in HR+/HER2– Breast Cancer


An analysis of real-world outcomes in a cohort of patients treated in mostly community settings showed that palbociclib plus letrozole improved both progression-free and overall survival in women with hormone receptor–positive, HER2-negative metastatic breast cancer.

Data published in Breast Cancer Research showed real-world efficacy of palbociclib (Ibrance) in combination with letrozole in women with hormone receptor–positive, HER2-negative metastatic breast cancer versus letrozole alone.1

These findings which showed extended overall and progression-free survival (PFS) benefit with the combination represents the first comprehensive comparative effectiveness analysis of outcomes for a CDK4/6 inhibitor in clinical practice.

“Real-world evidence is woven into the fabric of how we innovate and advance care for patients with breast cancer, supporting our randomized clinical trials,” Chris Boshoff, MD, PhD, Chief Development Officer, Oncology, Pfizer Global Product Development, said in a press release.2 “With more than 6 years of patient experience, a positive benefit-risk profile, strong clinical data, and robust real-world data, the totality of evidence solidifies the role of [palbociclib] plus endocrine therapy as a treatment for patients with [hormone receptor–positive, HER2-negative] metastatic breast cancer.”

The retrospective observational analysis of electronic health records within the Flatiron Health Analytic Database from 1430 patients with 3 months of follow-up or more were used in the study. Median follow-up was 24.2 months (interquartile range [IQR], 12.7-34.3) in those receiving palbociclib (n = 772) versus 23.3 months (IQR, 12.7-34.3) with letrozole (n =658).

Of note, 94% of the patient records included in the analysis were from those treated in the community setting. Clinical characteristics differed between the 2 groups, with the palbociclib group being younger and having better performance scores, a higher incidence of visceral disease, and a greater number of metastatic sites. Given these differences, stabilized inverse probability treatment weighting was implemented to balance baseline demographics.

The palbociclib plus letrozole combination was associated with a longer median real-world PFS at 20.0 months versus 11.9 months with letrozole alone (HR, 0.58; 95% CI, 0.49-0.69; P <.0001), with consistent benefit seen across subgroups. The median overall survival (OS) was not reached with palbociclib compared with 43.1 months with letrozole (HR, 0.66; 95% CI, 0.53-0.82; P = .0002). The rate of OS at 2 years was 78.3% versus 68.0% for the palbociclib and letrozole alone groups, respectively.

“Real-world evidence is increasingly used to complement traditional randomized clinical trial data to better understand a therapy’s effectiveness in routine clinical practice and inform treatment decisions,” Angela DeMichele, MD, lead researcher and Professor in Breast Cancer Excellence in the Perelman School of Medicine at the University of Pennsylvania, said in a press release. “The findings from this landmark real-world study align with the positive impact that I have seen in my own patients treated with palbociclib combination therapy.”

Data from this study are consistent with data from the phase 3 PALOMA-2 trial (NCT01740427), which compared palbociclib with palbociclib plus letrozole as initial endocrine-based therapy in postmenopausal women with estrogen receptor–positive metastatic breast cancer. The results of that trial served as the rationale for the approval of palbociclib and an aromatase inhibitor as therapy for women in this setting in 2016.3

Key differences between to 2 trials include that the real-world study is limited by a lack of randomization lack of uniform timing or type of clinical assessments and challenges with missing data. OS data are still being collected from the PALOMA-2 trial but are not yet mature.


1. DeMichele A, Cristofanilli M, Brufsky A, et al. Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2- metastatic breast cancer in US real-world clinical practice. Breast Cancer Res. 2021;23(1):37. doi: 10.1186/s13058-021-01409-8

2. Real-World Evidence Supports Effectiveness of First-line Ibrance (palbociclib) Combination Therapy in HR+, HER2- Metastatic Breast Cancer. News release. Pfizer. March 25, 2021. Accessed April 7, 2021.

3. Ibrance (palbociclib) receives approval in European Union for the treatment of women with HR+/HER2- metastatic breast cancer. News release. Pfizer. November 9, 2016. Accessed April 7, 2021.

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