Ashley M Hopkins1, Andrew Rowland2, Jessica M Logan3, Michael J Sorich2. 1. College of Medicine and Public Health, Flinders University, Flinders Drive, Bedford Park, Adelaide, South Australia, 5042, Australia. Electronic address: ashley.hopkins@flinders.edu.au. 2. College of Medicine and Public Health, Flinders University, Flinders Drive, Bedford Park, Adelaide, South Australia, 5042, Australia. 3. Mechanisms in Cell Biology and Disease Research Group, School of Pharmacy and Medical Sciences, Cancer Research Institute, University of South Australia, Adelaide SA 5000, Australia.
Abstract
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 = 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 (≤2 versus > 2) and ECOG performance-status (0 versus ≥ 1) (P < 0.05). Based on these two factors, patients can be characterised as one of three prognostic groups (good = 0 factors; intermediate = 1 factor; poor = 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: 36-48), 25 (23-30) and 16 (14-19) months, respectively, and median PFS was 12 (10-15), 8 (7-9) and 6 (4-7) 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.
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 = 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 (≤2 versus > 2) and ECOG performance-status (0 versus ≥ 1) (P < 0.05). Based on these two factors, patients can be characterised as one of three prognostic groups (good = 0 factors; intermediate = 1 factor; poor = 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: 36-48), 25 (23-30) and 16 (14-19) months, respectively, and median PFS was 12 (10-15), 8 (7-9) and 6 (4-7) 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.
Authors: Jennifer A Ligibel; Luke Huebner; Hope S Rugo; Harold J Burstein; Debra L Toppmeyer; Carey K Anders; Cynthia Ma; William T Barry; Vera Suman; Lisa A Carey; Ann H Partridge; Clifford A Hudis; Eric P Winer Journal: JNCI Cancer Spectr Date: 2021-04-12