Palbociclib/Letrozole Improves Survival in HR+ Metastatic Breast Cancer


Palbociclib in combination with endocrine therapy resulted in improved survival outcomes in a real-world population of patients with hormone receptor–positive, HER2-negative, metastatic breast cancer vs letrozole alone in the first-line setting.

Palbociclib (Ibrance) in combination with endocrine therapy resulted in improved survival outcomes in a real-world population of patients with hormone receptor (HR)–positive, HER2-negative, metastatic breast cancer vs letrozole alone in the first-line setting, according to data from a retrospective observational analysis published in Breast Cancer Research.1

At a median follow-up of 24.2 months, and after balancing for baseline demographic and clinical characteristics, the median real-world progression-free survival (rwPFS) was significantly longer with the palbociclib combination compared with letrozole alone, at 20.0 months vs 11.9 months, respectively (HR, 0.58; 95% CI, 0.49-0.69; P <.0001).

Additionally, the median overall survival (OS) had not been reached in the palbociclib arm vs 43.1 months in the letrozole-alone arm (HR, 0.66; 95% CI, 0.53-0.82; P =.0002). The 2-year OS rates were 78.3% and 68.0% in the investigative and control arms, respectively.

“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 of Oncology at Pfizer Global Product Development, stated 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 HR-positive, HER2-negative metastatic breast cancer.”

The goal of the retrospective observational analysis was to provide real-world evidence on the efficacy of the combination of palbociclib and letrozole compared with letrozole alone in a large cohort of patients from across the United States in routine clinical practice.

The analysis was conducted through the use of electronic health records within the Flatiron Health Analytic Database. Investigators identified a total of 1430 women with HR-positive, HER2-negative metastatic breast cancer who started either palbociclib/letrozole (n = 772) or letrozole alone (n = 658) as their frontline treatment between February 3, 2015, and February 28, 2019. The majority, or 94.0%, of patients were from the community setting, while 6.0% were from the academic setting.

Notably, the demographic and clinical characteristics between the 2 arms evaluated differed. Patients on the palbociclib arm were younger, had a better performance status, a higher incidence of visceral disease, and more metastatic sites, than those on the letrozole-only arm. After stabilized inverse probability treatment weighting (sIPTW) adjustment, patient characteristics were well balanced.

After sIPTW adjustment, the mean age of patients was 66.8 years vs 67.1 years in the investigative and control arms, respectively. Additionally, about 68.0% of patients in both arms were White. The median duration of follow-up in the palbociclib and letrozole-alone arms was 24.2 months and 23.3 months, respectively.

Results from a sensitivity analysis using the propensity score matching (PSM) method (n = 928) showed that the median rwPFS was also significantly extended with the palbociclib regimen over letrozole alone, at 20.2 months (95% CI, 18.2-23.7) vs 11.9 months (95% CI, 10.4-14.5), respectively (HR, 0.54; 95% CI, 0.46-0.65; P <.0001). Palbociclib/letrozole showcased a consistent PFS benefit compared with letrozole alone, across all subgroups analyzed.

Additional OS data showed that more patients on the letrozole-alone arm died (n = 266; 40.4%) than those in the palbociclib arm (n = 210; 27.2%). Using PSM as a sensitivity analysis, the median OS in the letrozole-alone arm was 43.1 months (95% CI, 34.2–not estimable) and had not been reached in the palbociclib/letrozole arm (HR, 0.58; 95% CI, 0.46-0.73; P <.0001). Again, additional analyses of OS revealed that the benefit achieved with the palbociclib combination over letrozole alone was generally observed across all subgroups examined.

Approximately 56% of patients in the investigative arm and about 67% of those in the control arm had available data pertaining to second-line treatment. Of those with available information, 42.2% in the palbociclib arm and 62.9% in the letrozole-alone arm went on to receive a CDK4/6 inhibitor as second-line treatment; 25.6% and 9.4%, respectively, went on to receive chemotherapy in the second line.

Data from the analysis proved to be consistent with data from the phase 3 PALOMA-2 trial (NCT01740427), which evaluated palbociclib in combination with letrozole vs placebo/letrozole as initial endocrine-based therapy in post-menopausal women with estrogen receptor–positive, HER2-negatgive metastatic breast cancer.

“Although findings from the PALOMA trials demonstrate the efficacy of palbociclib among patients who met study inclusion and exclusion criteria, real-world evidence of effectiveness provides further support for clinical decision-making in patients encountered in routine clinical practice,” the study authors concluded. “In this comparative effectiveness analysis, first-line palbociclib plus letrozole was associated with longer rwPFS and OS than letrozole alone in a heterogeneous population and among various patient subgroups.”


  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 Inc. March 25, 2021. Accessed March 25, 2021.

This article was originally published on OncLive as, "First-Line Palbociclib/Letrozole Shows Real-World Survival Benefit in HR+ Metastatic Breast Cancer."

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