Abstract P1-18-20: Real-world effectiveness of palbociclib plus letrozole vs letrozole alone for metastatic breast cancer with lung/liver metastases: Flatiron database analysis
Authors: Brufsky Adam , Liu Xianchen , Li Benjamin , McRoy Lynn , Layman Rachel M. 
Published: March 2022

Abstract
Background: CDK4/6 inhibitor in combination with endocrine therapy has become standard of care for patients with HR+/HER2- advanced/metastatic breast cancer (MBC), including those with visceral metastases. Although clinical trials and growing real-world evidence have demonstrated safety and effectiveness of CDK4/6i plus endocrine therapy for HR+/HER2- MBC, there is limited data on treatment patterns and effectiveness in patients with lung or liver metastases in routine clinical practice. This study compared real-world progression free survival (rwPFS) and overall survival (OS) of palbociclib plus letrozole (PB+LE) vs letrozole alone (LE) in HR+/HER2- MBC patients with lung or liver metastases in US routine clinical practice. Methods: This was a retrospective observational cohort study of MBC patients from the Flatiron Health longitudinal database, which contains electronic health records from over 280 cancer clinics representing more than 2.2 million actively treated cancer patients in the US. Between February 2015 and February 2019, 551 HR+/HER2- MBC women with lung or liver metastases started PB+LE or LE as first-line therapy. Patients were evaluated from start of PB+LE or LE to May 31, 2019 (data cutoff date), death, or last visit, whichever came first. rwPFS was defined as months from start of PB+LE or LE to death or disease progression, assessed based on clinical assessment or radiographic scan/tissue biopsy. Cox proportional-hazards models were used to estimate the relative effectiveness of PB+LE vs LE without and with adjustment of baseline demographics and clinical characteristics. Results: Of the 551 eligible patients, 353 (64.1%) had lung metastases, 123 (22.3%) had liver metastases, and 75 (13.6%) had both. A total of 330 (59.9%) patients were treated with PB+LE and 221 (40.1%) were treated with LE. Median age was 66.0 years in PB+LE patients and 71.0 years in LE patients, respectively. PB+LE patients were more likely to have ≥3 metastatic sites than LE patients (43.9% vs 37.1%). Median follow-up was similar between PB+LE and LE patients (22.6 vs 22.1 months). Median rwPFS was 15.4 months (95%CI = 12.5 - 19.5) in PB+LE patients and 10.2 months (95%CI=8.0-11.7) in LE patients (HR=0.60, 95%CI=0.49-0.74, p &lt;0.0001; Adjusted HR=0.56, 95%CI=0.45-0.71, p &lt;0.0001). Median OS was not reached (NR, 95%CI (38.3-NR)) in PB+LE patients vs 29.4 months (95%CI=25.8-40.8) in LE patients (HR=0.56, 95%CI=0.43-0.74, p &lt;0.0001; Adjusted HR=0.61, 95%CI=0.45-0.82. p&lt;0.0001). Table 1 presents key patient characteristics and rwPFS and OS results. Conclusions: This real-world comparative analysis provides evidence that palbociclib in combination with letrozole is associated with improved outcomes compared to letrozole alone for HR+/HER2- MBC patients with lung or liver metastases in the first-line setting. Further comparative effectiveness research of CDK4/6i combination vs endocrine therapy with more patients and longer follow-up is warranted in MBC patients with various visceral metastases.
Table. Patient characteristics and effectiveness outcomesVariablePB+LE (N=330)LE alone (N=221)White, n (%)219 (66.4)146 (66.1)Median age (IQR), years66.0(58.0-73.0)71.0 (62.0-80.0)Metastatic sites≥3, n (%)145 (43.9)82 (37.1)Lung metastases, n (%)207 (62.7)146 (66.1)Liver metastases, n (%)73 (22.1)50 (22.6)Liver and lung metastases, n (%)50 (15.2)25 (11.3)Brain metastases, n (%)14 (4.2)14 (6.3)rwPFS rate at 6 months, %76.263.2rwPFS rate at 12 months, %57.441.5rwPFS rate at 18 months, %44.832.8rwPFS rate at 24 months, %38.522.4Median PFS (95%CI), months15.4 (12.5-19.5)10.2 (8.0-11.7)OS rate at 12 months, %89.475.0OS rate at 24 months, %75.060.4OS rate at 36 months, %59.744.5Median OS (95%CI), monthsNR (38.3-NR)29.4 (25.8-40.8)Median follow-up, months (IQR)22.6 (13.9-31.2)22.1 (10.0-31.4)PB+LE= Palbociclib plus letrozole; LE= Letrozole alone; IQR= Interquartile range; NR=Not reached; rwPFS=Real-world progression free survival; OS= Overall survival
Citation Format: Adam Brufsky, Xianchen Liu, Benjamin Li, Lynn McRoy, Rachel M. Layman. Real-world effectiveness of palbociclib plus letrozole vs letrozole alone for metastatic breast cancer with lung/liver metastases: Flatiron database analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-20.