Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2\u2212 metastatic breast cancer in US real-world clinical practice

Angela Demichele,Rachel M Layman,Jack Mardekian,Hope S Rugo,Mylin A Torres,Xianchen Liu,Adam Brufsky,Massimo Cristofanilli,Richard S Finn,Lynn Mcroy,Birol Emir

doi:10.1186/s13058-021-01409-8

Abstract

BackgroundFindings from randomized clinical trials may have 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 methodsThis was a retrospective observational analysis of electronic health records within the Flatiron Health Analytic Database. A total of 1430 patients with ≥ 3 months 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 analyzed.ResultsAfter sIPTW adjustment, median follow-up was 24.2 months (interquartile range [IQR], 14.2–34.9) in the palbociclib group and 23.3 months (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 months; hazard ratio [HR], 0.58; 95% CI, 0.49–0.69; P < 0.0001). Median OS was not reached in the palbociclib group and was 43.1 months with letrozole alone (HR, 0.66; 95% CI, 0.53–0.82; P = 0.0002). 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.ConclusionsIn 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 registrationClinicaltrials.gov; NCT04176354

Highlights

Findings from randomized clinical trials may have limited generalizability to patients treated in routine clinical practice
Current treatment guidelines recommend the addition of a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in combination with endocrine therapy for the treatment of patients with hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2−) metastatic breast cancer (MBC) based upon multiple prospective randomized phase III trials in the first- and second-line setting [3,4,5]
Using electronic health records from the large multicenter Flatiron Health Analytic Database, we found that first-line palbociclib plus letrozole was associated with significantly longer Real-world progression-free survival (rwPFS) and overall survival (OS) than letrozole alone after Stabilized inverse probability treatment weighting (sIPTW)

Summary

Introduction

Findings from randomized clinical trials may have 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. Current treatment guidelines recommend the addition of a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in combination with endocrine therapy for the treatment of patients with hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2−) MBC based upon multiple prospective randomized phase III trials in the first- and second-line setting [3,4,5]. Not statistically significant, palbociclib plus fulvestrant was associated with a longer median OS than placebo plus fulvestrant in PALOMA-3 (34.9 vs 28.0; hazard ratio, 0.81 [95% CI, 0.64–1.03]; P = 0.09), preserving the 7-month improvement in progression-free survival (PFS) [15]. The OS data for PALOMA-2 are not yet available

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