Comparative Effectiveness of Palbociclib Plus Letrozole Vs Letrozole for Metastatic Breast Cancer in US Real-World Clinical Practices

Background Palbociclib, the first clinically available oral CDK4/6 inhibitor, in combination with endocrine therapy has become standard of care for HR+/HER2- advanced/metastatic breast cancer (MBC). No real-world studies have examined relative effectiveness of palbociclib plus endocrine therapy compared with endocrine therapy alone. This study compared real-world progression free survival (rwPFS) of palbociclib plus letrozole (PB+LE) vs letrozole alone (LE) for MBC in US routine clinical practices. Methods We conducted a retrospective analysis of MBC patients from the Flatiron Health longitudinal database, which contains electronic health records from 275 cancer clinics representing more than 2 million actively treated cancer patients in the US. Between February 2015 and August 2018, 1416 HR+/HER2– MBC women started PB+LE (n = 798) or LE (n = 618) as first-line therapy. Patients were evaluated from start of PB+LE or LE to November 2018, death, or last visit, whichever came first. rwPFS was defined as months from start of PB+LE or LE to death or disease progression based on clinical assessment or evidence by radiographic scan/tissue biopsy. 1:1 propensity score (PS) matching was used to balance patient characteristics. Results Of 1416 eligible patients, 906 were 1:1 PS matched (453 for each cohort). Median follow-up was 16.8 months, median age was 68.0 years, 70% were white, and 49.7% had visceral disease. Median rwPFS was 24.5 months (95%CI = 20.7 – 32.7) in PB+LE cohort and 17.1 months (95%CI=13.7—19.8) in LE cohort (HR = 0.68, 95%CI=0.56—0.84, p =.0003). Table presents key patient characteristics and landmark rwPFS rates. Conclusions The first comparative analysis of a CDK4/6 inhibitor in combination with endocrine therapy compared to endocrine therapy alone provides real-world evidence confirming the findings of PFS benefit demonstrated in clinical trial data for palbociclib in diverse clinical practices. Table . 329P Patient characteristics and real-world progressionfree survival (rwPFS) Variable PB+LE (N = 453) LE alone (N = 453) Median age (years) 68.0 68.0 White (%) 69.8 70.6 Median number of metastatic sites (n) 2.0 2.0 Bone only disease (%) 26.9 32.2 Visceral disease (%) 49.7 49.7 Median rwPFS, months (95%CI) 24.5 (20.7—32.7) 17.1 (13.7—19.8) rwPFS rate at 6 months (%) 82.8 74.5 rwPFS rate at 12 months (%) 72.1 58.9 rwPFS rate at 18 months (%) 60.1 48.4 rwPFS rate at 24 months (%) 50.2 39.1 Median follow-up, months (IQR) 16.8(8.1—27.1) 16.8(6.9—26.9) PB+LE = Palbociclib plus letrozole; LE = Letrozole alone; IQR = Interquartile Range Legal entity responsible for the study Pfizer Inc. Funding Pfizer Inc. Disclosure R.M. Layman: Research grant / Funding (institution): Pfizer Inc. X. Liu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. J. Mardekian: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. L. McRoy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc.