Abstract P1-19-02: Overall survival for first-line palbociclib plus letrozole vs letrozole alone for HR+/HER2- metastatic breast cancer patients in US real-world clinical practice
Authors: DeMichele Angela , Cristofanilli Massimo , Brufsky Adam , Liu Xianchen , Mardekian Jack , McRoy Lynn , Layman Rachel M , Rugo Hope S , Finn Richard S 
Published: March 2020

Abstract
Background: Palbociclib (PB), 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). The phase III PALOMA-2 trial demonstrated significant progression-free survival benefit of PB plus letrozole (LE) vs LE + placebo (27.6 vs 14.5 months; HR=0.56, 0&lt;.0001). Recent real-world descriptive studies support the clinical benefit of PB in routine clinical practice, however little is known about relative effectiveness of PB+LE vs LE alone in the real-world clinical setting. This study compared overall survival of MBC patients treated with PB+LE vs LE in a cohort of US routine clinical practices. Methods: We conducted a retrospective, observational analysis of MBC patients from the Flatiron Health’s nationwide longitudinal, demographically and geographically diverse database, which contains electronic health records (EHR) from over 280 cancer clinics (~800 sites of care) representing more than 2.2 million actively treated cancer patients in the US. Between February 2015 and February 2019, 1388 HR+/HER2- MBC adult women were treated on PB+LE (n=766) or LE (n=622) as first-line therapy as per physician’s choice. Patients were evaluated from start of PB+LE or LE to May 2019, death, or last visit, whichever came first. Overall survival was derived from a recent mortality data set generated by combining multiple data sources and benchmarked against the National Death Index. Inverse probability treatment weighting (IPTW) was used to balance baseline demographics and clinical characteristics and to adjust analyses for differences in observed potential confounders between PB+LE and LE cohorts. Cox proportional hazards analyses adjusted for weighted stabilized IPTW scores were used to compare the risk of overall survival (OS) between the 2 treatment groups. Results: Of the 1388 eligible patients, median age was 67.0 years, 68.2% were white, 40.6% were de novo MBC, 51.3% had visceral disease (lung or liver), 29.3% had bone-only disease, and 94.5% were treated in community oncology practices. Median follow-up was 22.0 months for PB+LE cohort and 19.0 months for LE cohort. As of May 2019, there were 337 OS events (183 in LE cohort vs 154 in PB+LE cohort). The estimated OS rates for PB+LE and LE cohorts based on the Kaplan Meier weighted curve were 81.2% and 70.8% at 24 months, and 72.0% and 60.6% at 36 months, respectively. The IPTW adjusted HR was 0.62 (95%CI=0.49—0.78, p&lt;.0001). Table 1 presents key patient characteristics and estimated OS rates in PB+LE and LE cohorts. Conclusions: This real-world comparative effectiveness analysis demonstrates significant overall survival benefit of first line palbociclib in combination with letrozole compared to letrozole therapy alone among patients with HR+/HER2- metastatic breast cancer. Acknowledging the limitations of this non-randomized EHR database analysis, these data support the value of palbociclib when added to letrozole in improving long-term outcomes in the real-world setting. Funding: Pfizer Inc.
Table 1. Patient characteristics and overall survival (OS)VariablePB+LELE alone(N=766)(N=622)Median age (IQR), years66.0 (58.0—73.0)70.0 (61.0—79.0)White (%)68.368.0Median number of metastatic sites (n)2.02.0Bone-only disease (%)27.731.2Visceral disease (%)52.949.4De novo MBC (%)41.539.4Median follow-up (95%CI), months 22.0 (20.5—23.7)19.0 (16.7—21.2)Percent of events censored (%)79.970.6Estimated OS rate (%)6 months95.988.912 months91.384.624 months81.270.836 months72.060.6PB+LE= Palbociclib plus letrozole; LE= Letrozole alone; CI = Confidence interval; IQR = interquartile range
Citation Format: Angela DeMichele, Massimo Cristofanilli, Adam Brufsky, Xianchen Liu, Jack Mardekian, Lynn McRoy, Rachel M Layman, Hope S Rugo, Richard S Finn. Overall survival for first-line palbociclib plus letrozole vs letrozole alone for HR+/HER2- metastatic breast cancer patients in US real-world clinical practice [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-02.