First-Line Treatment with a Cyclin-Dependent Kinase 4/6 Inhibitor Plus an Aromatase Inhibitor for Metastatic Breast Cancer in Alberta

Abstract

In this analysis, we describe population-based outcomes for first-line treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) combined with an aromatase inhibitor (AI). All patients who were prescribed CDK4/6i + AI from January 2016 through June 2019 were included. Patient demographics, tumour and treatment characteristics were collected and described. Survival distributions were estimated using the Kaplan–Meier method. Multivariate analysis (MVA) was constructed to examine associations between potentially prognostic clinical variables and progression-free survival (PFS). In total, 316 patients were included. The median age was 61 years. After a median follow-up of 28.1 months, the median PFS was 37.9 months (95% CI, 26.7–NR). In the MVA, PR-negative tumour (HR, 2.37; 95% CI, 1.45–3.88; p = 0.001) and CDK4/6i dose reduction (HR, 1.51; 95% CI, 1.06–2.16; p = 0.022) predicted worse PFS. Median overall survival (OS) was not reached. The 30-month and 36-month OS rates were 74% and 68%, respectively. Of patients who progressed, 89% received second-line treatment. Median time to progression on second-line chemotherapy was 9.0 (5.8–17.6) months, and median time to progression on second-line hormonal therapy +/− targeted agent was 4.0 (3.4–8.6) months (p = 0.012). CDK4/6i + AI as first-line treatment for HR-positive, HER2-negative MBC in Alberta is justified based on favourable PFS and early OS outcomes.

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

“…This retrospective real-world study utilized the Syapse LHN to identify patients with HR+/HER2− A/MBC who were treated with palbociclib plus an aromatase inhibitor as first-line therapy. Findings from this study indicate treatment patterns and effectiveness outcomes with palbociclib plus aromatase inhibitor combination therapy are similar to what has been observed in other EHR real-world studies and complement data from randomized controlled trials [ 8 , 9 , 11 , 19 , 26 , 27 , 28 , 29 , 30 ]. After a median follow-up duration of 22.4 months, median rwPFS was 31.7 months and the estimated OS rate at 2 years was 78.0%.…”

“…Previous real-world studies showed a median rwPFS between 15.1 and 37.9 months with palbociclib combination therapy as first-line therapy for HR+/HER2− A/MBC [ 19 , 26 , 27 , 28 , 29 , 30 ]. The median rwPFS outcome observed in the current real-world study is longer than some PFS estimates previously reported; this may be due in part to the better overall prognostic characteristics of the patients in this cohort, with a larger proportion of patients with de novo disease and bone-only disease, which tends to be associated with longer PFS [ 32 ].…”

The Impact of Real-World Alternative Dosing Strategies of Palbociclib on Progression-Free Survival in Patients with Metastatic Breast Cancer

“…Overall, our results with both letrozole and fulvestrant suggest a substantial benefit of palbociclib on PFS in women with HR-positive, HER2−negative metastatic breast cancer in a Canadian context, as observed in the existing literature [17][18][19][20][21][22][23][24][25][26][27].…”

“…The findings of this study contribute to the growing literature of real-world evidence with palbociclib from a Canadian context [17,18,32]. To the best of our knowledge, this is one of the first studies of its kind designed to investigate the effect of alternative dosing strategies on progression-free survival.…”

“…In real-world settings, oncologists have deviated from conventional monograph dosing recommendations and varied their prescribing strategies in attempts to mitigate neutropenic effects, hoping to maintain palbociclib tolerability and extend overall treatment duration. Recent studies have reported real-world outcomes and described dosing modifications trends [17][18][19][20][21][22][23][24][25][26][27]. However, to the best of our knowledge, this is the first real-world study assessing the direct impact of palbociclib off-monograph dosing modifications on PFS.…”