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At the 2019 ASCO (American Society of Clinical Oncology) Annual Meeting, several interesting trial results were presented in the field of HER2-positive metastatic breast cancer. The end-of-study analysis of the pivotal CLEOPATRA trial indicated an overall survival of 57.1 months in patients receiving pertuzumab in addition to trastuzumab and docetaxel in the first-line setting. SOPHIA was the first phase III trial comparing the Fc-engineered antibody margetuximab plus chemotherapy by physician’s choice with trastuzumab plus chemotherapy in heavily pretreated patients; the novel antibody yielded a statistically significant albeit short prolongation of progression-free survival (PFS) over standard treatment. The phase III NALA trial compared the second-generation tyrosine-kinase inhibitors neratinib with lapatinib; both drugs were combined with capecitabine. In this study a clinically meaningful prolongation of PFS by 2.2 months was observed. In addition, the time to intervention for brain metastases was prolonged in the neratinib group and the cumulative incidence of brain metastases was lower as well. On the downside a high rate of grade 2 and 3 diarrhoea was observed.