Trastuzumab Combined with Pegylated Liposomal Doxorubicin in Patients with Metastatic Breast Cancer

<i>Objective:</i> Combination of trastuzumab and anthracyclines in metastatic breast cancer (MBC) is precluded due to cardiotoxicity. Pegylated liposomal doxorubicin (PLD) is the least cardiotoxic among the anthracyclines. We performed a phase II study of trastuzumab and PLD with biomarker evaluation. <i>Methods:</i> Patients with MBC and HER2 overexpression, assessed as 3+ at local laboratories, received trastuzumab 8 mg/kg as loading dose followed by 6 mg/kg in combination with PLD 30 mg/m², both given every 3 weeks. To be eligible, patients should have received first-line chemotherapy for MBC or should have relapsed within a year of adjuvant taxane. Tumor tissue blocks were collected for central review and exploratory biomarker evaluation. Left-ventricular ejection fraction (LVEF) was closely monitored by cardiac ultrasound. <i>Results:</i> Among 37 patients, an overall response rate of 22% was observed with a progression-free survival (PFS) of 6.5 months (0.8–31.1, 95% CI 2.7–10.3) and a survival of 18.7 months (1.6–40.8, 95% CI 3.7–33.7). No decline in LVEF was noticed. Overexpression of mTOR and TOP2A gene alterations were associated with better PFS. PTEN gene deletion was associated with resistance to treatment. <i>Conclusion:</i> Trastuzumab combined with PLD every 3 weeks is feasible, effective and safe in HER2-positive patients.