e18746 Background: Limited real-world data exists on the treatment of HER2+ metastatic breast cancer (mBC) following pertuzumab (P)+trastuzumab (T) based regimens in first-line (1L) setting. In the EMILIA trial, T-DM1 had higher median progression-free survival (mPFS) (9.6 months vs. 6.4 months) and median overall survival (mOS) (30.9 months vs. 25.1 months) than lapatinib plus capecitabine in patients previously treated with trastuzumab and a taxane. Real-world treatment effectiveness data following 1L P+T could complement clinical trial data to help inform understanding of unmet needs of HER2+ mBC patients requiring second-line (2L) treatment. Methods: IQVIA Oncology EMR (US) database was analyzed to identify adult patients with confirmed HER2+ mBC who were treated with a 1L P+T based regimen between Jan 2015-Sep 2019. An anti-HER2-based regimen might include hormonal therapy and/or chemotherapy. Eligible patients who had ≥60 days of follow-up since 1L P+T regimen initiation were included in outcomes assessment. Treatment discontinuation was defined as a treatment gap of at least 365 days, initiation of a new line of therapy, or death. Treatment failure was defined as the initiation of a new line of therapy or death. A new line of therapy was defined as the use of another anti-HER2 agent, switching to a different class of chemotherapy, or re-initiation of the same regimen after a gap of at least 365 days. Median duration of anti-HER2 regimen, median time to treatment failure (mTTF) and median overall survival (mOS) were estimated using Kaplan-Meier analysis. Results: A total of 710 patients were treated with a 1L P+T based regimen (median age: 57 years; 47% HR+, 26% HR- and 27% unknown HR status; 80% received a taxane). Median follow-up was 20.3 months. Median treatment duration for 1L P+T regimens was 15.3 months. A total of 302 patients (43%) discontinued 1L P+T treatment during the study, of which 222 patients received 2L therapy with a median follow-up of 9.6 months post 2L initiation. Among patients receiving 2L treatment, 214 (96%) received anti-HER2-based regimens. T-DM1 based regimens were most common (n = 159; 72%), followed by trastuzumab-based regimens (n = 29; 13%), lapatinib-based regimens (n = 13; 6%) and neratinib (n = 13; 6%). Overall, median 2L treatment duration was 5.9 months, mTTF was 8.6 months, and mOS was 25.4 months. For patients receiving T-DM1 as 2L therapy, median duration of T-DM1 treatment was 5.7 months, mTTF was 7.9 months, and mOS was 24.4 months. Conclusions: T-DM1 was the most common 2L treatment following 1L P+T based regimen for HER2+ mBC. Median TTF and mOS for T-DM1 in this study were numerically shorter than mPFS and mOS reported in the EMILIA trial, possibly due to the inclusion of a broader patient population beyond those studied in a clinical trial in the current study. There remains an unmet need of a more effective treatment for HER2+ mBC after 1L treatment.