Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2− metastatic breast cancer in US real-world clinical practice

Abstract

Background Findings from randomized clinical trials may\xa0have limited generalizability to patients treated in routine clinical practice. This study examined the effectiveness of first-line palbociclib plus letrozole versus letrozole alone on survival outcomes in patients with hormone receptor–positive (HR+)/human epidermal growth factor receptor–negative (HER2−) metastatic breast cancer (MBC) treated in routine clinical practice in the USA. Patients and methods This was a retrospective observational analysis of electronic health records within the Flatiron Health Analytic Database. A total of 1430 patients with ≥\u20093\u2009months of follow-up received palbociclib plus letrozole or letrozole alone in the first-line setting between February 3, 2015, and February 28, 2019. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. Real-world progression-free survival (rwPFS) and overall survival (OS) were\xa0analyzed. Results After sIPTW adjustment, median follow-up was 24.2 months\xa0(interquartile range [IQR], 14.2–34.9) in the palbociclib group and 23.3\xa0months (IQR, 12.7–34.3) in those taking letrozole alone. Palbociclib combination treatment was associated with significantly longer median rwPFS compared to letrozole alone (20.0 vs 11.9\u2009months; hazard ratio [HR], 0.58; 95% CI, 0.49–0.69; P \u2009<\u20090.0001). Median OS was not reached in the palbociclib group and was 43.1\u2009months with letrozole alone (HR, 0.66; 95% CI, 0.53–0.82; P \u2009=\u20090.0002). The 2-year OS rate was 78.3% in the palbociclib group and 68.0% with letrozole alone. A propensity score matching analysis showed similar results. Conclusions In this “real-world” population of patients with HR+/HER2− MBC, palbociclib in combination with endocrine therapy was associated with improved survival outcomes compared with patients treated with letrozole alone in the first-line setting. Trial registration Clinicaltrials.gov; NCT04176354