Evaluating the Relative Effectiveness of Palbociclib plus Letrozole in a Real-World Study

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When combined with endocrine therapy, CDK4/6 inhibitors have become the standard of care for patients with hormone receptor (HR)-positive, HER2-negative advanced/metastatic breast cancer, even including patients living with visceral metastases.

There exists a lack of data regarding patterns of treatment and their relative effectiveness in patients with lung or liver metastases in routine clinical practice, despite clinical trials and growing real-world evidence that have demonstrated the safety and effectiveness of CDK4/6 inhibitors plus endocrine therapy for HR-positive, HER2-negative metastatic breast cancer.

In routine clinical practice in the United States, an evaluation of overall survival and real-world progression-free survival of palbociclib plus letrozole (palbociclib + LET) compared with LET alone in patients living with HR-positive, HER2-negative metastatic breast cancer with lung or liver metastases was conducted.

The Flatiron Health longitudinal database, with electronic health records from >280 cancer clinics, representing more than 2.2 million actively treated cancer patients in the United States, was used so that patients with metastatic breast cancer could be included in the retrospective observational cohort study.

Conducted between February 2015 and February 2019, a total of 551 female patients with HR-positive, HER2-negative metastatic breast cancer and liver or lung metastases initiated first-line therapy with either palbociclib + LET or LET alone.

Patients were evaluated from the start of palbociclib + LET or LET alone to whichever came first—May 31, 2019, the data cutoff date, death, or last visit. The real-world progression-free survival was defined as months from initiation of palbociclib + LET or LET alone to death or disease progression, as assessed based on radiographic scan/tissue biopsy or clinical assessment.

The relative effectiveness of palbociclib + LET compared with LET alone with and without adjustment of baseline demographics and clinical characteristics was estimated.

Approximately 64.1% of the eligible patients had lung metastases, 2.32% had liver metastases, and 13.6% had both.

Approximately 40.1% of patients were treated with LET alone, and a total of 59.9% of patients were treated with palbociclib + LET. Correspondingly, the median age was 71.0 years in the LET-alone patient cohort and was 66.0 years in the palbociclib + LET patient cohort.

Patients who were receiving the combination of palbociclib + LET were more likely to have ≥3 metastatic sites than LET-alone patients at a rate of 43.9% compared with 37.1%.

When comparing these 2 groups, the median follow-up was similar between palbociclib + LET and LET-alone patients at a rate of 22.6 months compared with 22.1 months.

In palbociclib + LET patients, the median real-world progression-free survival was 15.4 months and in LET-alone patients it was 10.2 months.

Based on this real-world study for patients with HR-positive, HER2-negative metastatic breast cancer and lung or liver metastases in the first-line setting, the investigators concluded that palbociclib when combined with LET is associated with improved outcomes, compared with LET alone. Further studies are warranted to compare the effectiveness based on research focused on the CDK4/6 inhibitor combination compared with endocrine therapy. These future studies should include more patients and longer follow-up in metastatic breast cancer patients with a range of types of visceral metastases.


Brufsky A, Liu X, Li B, et al. Real-world effectiveness of palbociclib plus letrozole vs letrozole alone for metastatic breast cancer with lung/liver metastases: Flatiron database analysis. 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021. P1-18-20.

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