Long-term outcome with targeted therapy in advanced/metastatic HER2-positive breast cancer: The Royal Marsden experience.

Agents targeting the human epidermal growth factor receptor 2 (HER2) have improved outcomes of advanced HER2-positive breast cancer with durable responses. We evaluated first-line therapy long-term outcomes in patients responding for more than 1 year. We retrospectively identified patients on first-line anti-HER2 therapy at The Royal Marsden Hospital for at least 1 year from 2001 to 2016. Demographics, disease characteristics, treatments and adverse events were recorded. Simple statistics, Fisher's, Chi squared and log-rank tests were used. 208 patients on treatment for at least 1 year had a median age of 54 years (31-88). 38.0% had de novo metastatic disease and 55.9% were ER positive. Of the relapsed cases, 54.4% previously had trastuzumab. At the time of presentation of metastatic disease, 27.4% of the entire cohort had pulmonary, 43.7% liver and 10.6% brain involvement. 97.1% received trastuzumab and 1.44% lapatinib; 33.2% pertuzumab and trastuzumab. 82.7% received chemotherapy (usually taxanes). 47.6% received maintenance endocrine therapy. Median progression-free survival was 39.5 months and overall survival 81.0 months. Overall response rate was 87.5%. Cardiotoxicity occurred in 4.8% of cases. Seven patients stopped treatment electively after 17-87 months and, so far, all remain in complete remission. First-line anti-HER2 treatment is associated with median overall survival longer than 6 years in half of the patients free from disease progression after a year, but most still relapse eventually. Response prediction would be key to inform trial design and treatment decisions in this setting.