AbstractPurposeReal‐world data about pegylated liposomal doxorubicin (PLD) in patients with metastatic breast cancer (MBC) are limited. We have aimed to highlight the role of PLD in daily practice focusing on older patients and patients with comorbidities with MBC.MethodsWe analyzed electronic records of all patients with advanced/metastatic breast cancer treated with single‐agent PLD at the University Hospital Basel between 2003 and 2021. Primary endpoint was time to next chemotherapy or death (TTNC). Secondary endpoints were overall survival (OS), progression‐free survival (PFS), and overall response rate (ORR). We performed univariate and multivariate analysis for clinical variables.Results112 patients with MBC having received single‐agent PLD in any treatment line were analyzed, including 34 patient who were older than 70 years and 61 patients with relevant comorbidities. Median TTNC, OS, and PFS for treatment with PLD were 4.6, 11.9, and 4.4 months, respectively. ORR was 13.6%. Age >70 years predicted shorter OS (median 11.2 months) in multivariate analysis (hazard ratio [HR] 1.83, 95% CI 1.07–3.11,p= 0.026). Age and comorbidities did not significantly affect other endpoints. Unexpectedly, hypertension predicted longer TTNC (8.3 months,p= 0.04) in univariate analysis, maintained in multivariate analysis as a trend for both TTNC (HR 0.62,p= 0.07) and OS (HR 0.63,p= 0.1).ConclusionAge predicted shorter OS significantly but median OS was not relevantly shorter in older patients. PLD remains a treatment option in patients with comorbidities and older patients with MBC. However, our real‐world results of PLD appear underwhelming compared to relevant phase II trials through all age groups, pointing to an efficacy‐effectiveness gap, possibly due to sampling bias.