Real-World Treatment Patterns and Clinical Effectiveness of Palbociclib Plus an Aromatase Inhibitor as First-Line Therapy in Advanced/Metastatic Breast Cancer: Analysis from the US Syapse Learning Health Network

Abstract

This retrospective single-arm study assessed real-world treatment patterns and clinical outcomes in patients with hormone receptor—positive/human epidermal growth factor receptor 2—negative (HR+/HER2−) advanced/metastatic breast cancer (A/MBC) who received palbociclib plus an aromatase inhibitor as first-line therapy in US community health systems. Using electronic health records from the Syapse Learning Health Network, 242 patients were identified as having received first-line palbociclib plus an aromatase inhibitor between 3 February 2015, and 31 July 2019 (data cutoff 1 February 2020) resulting in a minimum potential 6-month follow-up period. In total, 56.6% of patients had de novo A/MBC at initial breast cancer diagnosis, 50.8% had bone-only disease, and 32.2% had visceral disease. Median follow-up was 22.4 months. Disease progression (26.4%) and intolerance/toxicity (14.9%) were the main reasons for treatment discontinuation. The median (95% CI) real-world progression-free survival was 31.7 (27.9—not estimable (NE)) months and 2-year estimated overall survival (OS) rate was 78.0%. In total, 25.6% of patients died; however, OS data are limited by the small population size and insufficient follow-up time. These real-world effectiveness outcomes complement findings from other real-world studies and randomized controlled trials and support palbociclib plus an aromatase inhibitor as first-line therapy for HR+/HER2− A/MBC.

HR+/HER2– de novo metastatic breast cancer: a true peculiar entity?

“…Additionally, in routine practice, the proportion of patients with dnMBC is much higher than that reported in epidemiological reports, with the number reaching up to 40% of the population observed. [72][73][74][75][76][77][78][79] One of the largest real-world studies derives data from the Flatiron's health longitudinal database, which includes de-identified electronic health records from more than 280 cancer clinics and represents 2.4 million patients with cancer treated in the USA. 72 This retrospective observational study included 1430 patients receiving first-line treatment with palbociclib and letrozole or letrozole alone for MBC from 2015 to 2019.…”

“…In this subgroup, mPFS was 38.8 months versus 30.5 in patients with rMBC. 77 A single US institution retrospective study including 222 patients with MBC treated with palbociclib and endocrine therapy (mostly AI) from 2015 to 2021 and including 29.7% with dnMBC, showed that this subgroup experienced an improved PFS as compared to those with recurrent disease. 78 In the analysis of the North Carolina University database, an improved PFS of nearly 14 months (25.5 versus 11.9) was observed in patients with dnMBC treated with any first-line therapy, which reached a 19-month difference in the small number of patients treated with CDK4/6i.…”

Palbociclib in Older Patients with Advanced/Metastatic Breast Cancer: A Systematic Review

“…Three retrospective studies using data from the Flatiron Health longitudinal database had different study time frames and populations (in terms of patient age); however, there remains a possibility of patient overlap across studies [ 35 , 37 , 52 ]. Older patients were defined as ≥ 60 years of age in one study [ 40 ], ≥ 65 years in 21 studies [ 30 , 32 , 34 , 36 – 39 , 42 , 43 , 45 , 46 , 49 , 50 , 52 , 53 , 56 – 58 , 64 , 65 , 68 ], ≥ 70 years in 11 studies [ 31 , 44 , 47 , 48 , 54 , 55 , 59 – 63 , 66 , 67 ], and ≥ 75 years in four studies [ 33 , 35 , 41 , 51 ]. Three studies evaluated CDK 4/6 inhibitors as a class; however, ≥ 80% of the patients received palbociclib as the CDK 4/6 inhibitor [ 43 , 58 , 67 ].…”

“…Of the included 37 RWE studies, seven included only older patients [ 37 , 41 , 43 , 59 – 63 ]. Among RWE studies including both younger and older patients, six studies provided data on the proportion of patients aged ≥ 75 years (31% [1960 of 6380]) [ 36 , 37 , 45 , 46 , 51 , 52 ]. Data from a total of 12 studies for patient demographics and baseline characteristics in older patients who received palbociclib were limited and heterogeneous (most studies only described the total patient population).…”

“…In 16 studies, there was no significant difference in real-world progression-free survival (rwPFS) between younger and older patients who received treatment with palbociclib [ 34 , 38 , 39 , 46 – 49 , 51 – 53 , 55 , 56 , 58 , 59 , 65 , 67 , 68 ]. In three studies, rwPFS benefit was comparable between younger and older patients; however, no test for significance was conducted [ 45 , 50 , 66 ]. In one study, rwPFS rate at 12 months was significantly longer in patients ≥ 65 years of age versus patients aged < 65 years [ 64 ].…”