Real-world palbociclib dose modifications and clinical outcomes in patients with HR+/HER2-metastatic breast cancer: A Flatiron Health database analysis

Purpose: To examine the associations of palbociclib dose modifications with clinical outcomes of patients with HR+/HER2metastatic breast cancer (MBC) treated with first-line (1L) palbociclib + aromatase inhibitor (AI) in routine practice. Methods: Using the Flatiron Health Analytic Database, we conducted a retrospective analysis of HR+/HER2MBC patients who started 1L palbociclib + AI February 2015-March 2020. Kaplan-Meier analyses were used to estimate treatment duration, real-world progression-free survival (rwPFS), and overall survival (OS) by palbociclib dose adjustments (any change in palbociclib daily dose while on treatment) and dose reductions (starting dose <125 mg/day or dose reduced while on treatment). Cox proportional hazard regression models were performed to compute unadjusted/adjusted hazard ratios (HRs). Results: Of 1302 patients with documented starting dose, 524 (40.2 %) had palbociclib dose adjustments; 778 (59.8 %) had none. Median treatment duration was significantly longer in patients with dose adjustments versus those with none (27.4 vs 21.4 months; adjusted HR = 0.80 [95 % CI, 0.69-0.93]; P = 0.004). Patients with and without dose adjustments showed similar median rwPFS (20.5 vs 19.6 months; adjusted HR = 0.89 [95 % CI, 0.76-1.04]; P = 0.133). Median OS was significantly prolonged in patients with versus without dose adjustments (57.8 vs 51.4 months; adjusted HR = 0.73 [95 % CI, 0.59-0.89]; P = 0.002). Similar findings were observed in patients with and without dose reductions. Conclusions: In this real-world study, rwPFS in HR+/HER2MBC patients was maintained irrespective of dose adjustments. However, dose adjustments were associated with extended treatment duration and OS.