Primary predictors of survival outcomes for HER2-positive advanced breast cancer patients initiating ado-trastuzumab emtansine

Objectives: Common therapies for HER2-positive advanced breast cancer (ABC) are associated with heterogeneity in prognosis and treatment benefit. Prognostic models of survival outcomes with ado-trastuzumab-emtansine (T-DM1) have not been evaluated.Material and methods: A pre-treatment prognostic model for overall survival (OS) and progression-free survival (PFS) based on clinicopathological factors was developed for HER2-positive ABC patients initiating second-line and later T-DM1 using data from the randomised clinical trials EMILIA and TH3RESA(n ¼ 893). Pre-treatment prognostic groups were identified via recursive partitioning analysis.Results: The most significant OS/PFS pre-treatment risk predictors were metastatic sites count (( ≤ 2versus > 2) and ECOG performance-status (0 versus ≥ 1) (P < 0.05). Based on these two factors, patient scan be characterised as one of three prognostic groups (good ¼ 0 factors; intermediate ¼ 1 factor;poor ¼ 2 factors). The prognostic groups were identified as significantly associated with OS (P < 0.001)and PFS (P < 0.001). Median OS for the good, intermediate and poor prognostic groups were 40 (95%CI:36e48), 25 (23e30) and 16 (14e19) months, respectively, and median PFS was 12 (10e15), 8 (7e9) and 6(4e7) months.Conclusion: Pre-treatment prognostic groups with significant differences in OS and PFS for HER2-positive ABC patients initiating second-line and later T-DM1 were identified. For HER2-positive ABC patients considering initiating second-line and later T-DM1, the prognostic groups enable more personalized expectations of disease control, survival and absolute treatment benefit. Refereed/Peer-reviewed