[HTML][HTML] Molecular imaging as a tool to investigate heterogeneity of advanced HER2-positive breast cancer and to predict patient outcome under trastuzumab …
G Gebhart, LE Lamberts, Z Wimana, C Garcia… - Annals of oncology, 2016 - Elsevier
Annals of oncology, 2016•Elsevier
Background Only human epidermal growth factor receptor (HER) 2 status determined by
immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) has been
validated to predict efficacy of HER2-targeting antibody-drug-conjugate trastuzumab
emtansine (T-DM1). We propose molecular imaging to explore intra-/interpatient
heterogeneity in HER2 mapping of metastatic disease and to identify patients unlikely to
benefit from T-DM1. Patients and methods HER2-positive mBC patients with IHC3+ or …
immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) has been
validated to predict efficacy of HER2-targeting antibody-drug-conjugate trastuzumab
emtansine (T-DM1). We propose molecular imaging to explore intra-/interpatient
heterogeneity in HER2 mapping of metastatic disease and to identify patients unlikely to
benefit from T-DM1. Patients and methods HER2-positive mBC patients with IHC3+ or …
Background
Only human epidermal growth factor receptor (HER)2 status determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) has been validated to predict efficacy of HER2-targeting antibody-drug-conjugate trastuzumab emtansine (T-DM1). We propose molecular imaging to explore intra-/interpatient heterogeneity in HER2 mapping of metastatic disease and to identify patients unlikely to benefit from T-DM1.
Patients and methods
HER2-positive mBC patients with IHC3+ or FISH ≥2.2 scheduled for T-DM1 underwent a pretreatment HER2-positron emission tomography (PET)/computed tomography (CT) with 89Zr-trastuzumab. [18F]2-fluoro-2-deoxy-D-glucose (FDG)–PET/CT was performed at baseline and before T-DM1 cycle 2. Patients were grouped into four HER2–PET/CT patterns according to the proportion of FDG-avid tumor load showing relevant 89Zr-trastuzumab uptake (>blood pool activity): patterns A and B were considered positive (>50% or all of the tumor load ‘positive’); patterns C and D were considered negative (>50% or all of the tumor load ‘negative’). Early FDG–PET/CT was defined as nonresponding when >50% of the tumor load showed no significant reduction of FDG uptake (<15%). Negative (NPV) and positive predictive values (PPV) of HER2–PET/CT, early FDG response and their combination were assessed to predict morphological response (RECIST 1.1) after three T-DM1 cycles and time-to-treatment failure (TTF).
Results
In the 56 patients analyzed, 29% had negative HER2–PET/CT while intrapatient heterogeneity (patterns B and C) was found in 46% of patients. Compared with RECIST1.1, respective NPV/PPV for HER2–PET/CT were 88%/72% and 83%/96% for early FDG–PET/CT. Combining HER2–PET/CT and FDG–PET/CT accurately predicted morphological response (PPV and NPV: 100%) and discriminated patients with a median TTF of only 2.8 months [n = 12, 95% confidence interval (CI) 1.4–7.6] from those with a TTF of 15 months (n = 25, 95% CI 9.7–not calculable).
Conclusions
Pretreatment imaging of HER2 targeting, combined with early metabolic response assessment holds great promise for improving the understanding of tumor heterogeneity in mBC and for selecting patients who will/will not benefit from T-DM1.
ClinicalTrials.gov identifier
NCT01565200.
Elsevier
