240P Effect of dose intensity (DI) of palbociclib (PAB) and initial body weight dosage (BWD) on progression free survival (PFS): A real-world data analysis in patients with hormone-receptor (HR) positive HER2 negative metastatic breast cancer (MBC)

PAB’s standard fixed dose of 125 mg may result in a high variability in efficacy and toxicity profile. The objective of this study was to evaluate the effect of DI on PFS in patients(pts) with HR+, HER2-negative MBC in a real-world setting. Retrospective, longitudinal study for pts who started PAB as a 1st or 2nd line treatment at Catalan Institute of Oncology between Nov 2017-May 2021. DI was a ratio between the amount of PAB mg administered until disease progression or end of treatment and standard dosing (125mg daily for 3weeks on/1week off). DI was categorized as ≤80% and >80%. BWD of PAB was categorized as <2 mg/Kg and ≥2 mg/Kg. Adjustment factors were age, de novo MBC, line of treatment. Multivariate Cox regression model was used to estimate adjusted hazard ratios (aHRs) and 95% CIs. 220 pts were included, with a median follow-up of 22.8 months(m) for the primary endpoint (IR13.6–31.8m). Median age 63 years (IR 54–72.7) and PBC was 1st-line and 2nd-line treatment in 137(64.3%) and 45pts(21.1%), respectively. In 97.7% initial dose was 125mg/daily and median 1.9mg/Kg (IQR 1.6 – 2.2). Dosing reduction due to toxicity was required in 94pts (42.7%). Median DI along treatment was 88.7% (IR 74.8-98.1); 76 and 144pts were treated with DI ≤80% and >80%, respectively. Dose reduction due to grade III-IV neutropenia was higher in pts treated with DI ≤80% vs DI >80%: 84.2% vs 20.8% (p<0.001) and 93% vs 55.6% (p<0.001), respectively. At closing date, treatment was discontinued in 168pts (76.4%): 140 due to progression and 11 due to toxicity. Overall response rate was 76.1% vs 70.6% with DI ≤80% and >80%, respectively (17.9 vs 27.1% partial responses and 3 vs 4.7% complete responses). In the multivariate analysis, DI >80% (aHR 1.59, 95% CI: 1.06-2.39), PAB initial dose > 2mg/Kg (aHR 1.68, 95%: CI 1.15-2.44) and ≥2nd line therapy (aHR: 1.58; CI 1.08-2.31) were associated with higher risk of progression/death while de novo MBC was associated with lower risk (aHR 0.52, 95% CI: 0.32-0.87). In our study, PAB dosing <2mg/kg and a DI <80% were associated with lower risk of PFS in pts with HR+/HER2-negative MBC.