64Cu-DOTA-trastuzumab PET/CT to predict response to ado-trastuzumab emtansine (TDM1) in HER2-positive metastatic breast cancer.

Abstract

e12525 Background: Having demonstrated that 64Cu-DOTA trastuzumab is an effective PET imaging agent for HER2 positive (HER2+) breast cancer, we now evaluate the methodology for prediction of response and benefit from TDM1 in women with metastatic disease. Methods: Patients eligible to receive TDM1 as therapy were chosen on the basis of biopsy confirmed HER2+ disease, and at least 1 site of metastasis ≥ 2.0 cm outside the biopsy site. Pretreatment staging included 18F-FDG PET/CT. Prior to injection of 64Cu-DOTA-trastuzumab, patients received 45 mg of cold trastuzumab to reduce liver uptake. PET-CT scans were obtained at 16-28 h (Day1) and 39-49 h (Day 2) over fields of view chosen in reference to the 18F-FDG scans. TDM1 (3.6 mg/kg) was administered every 3 weeks. Restaging 18F-FDG PET/CT was performed every 2 cycles, and response to therapy was determined by PERCIST (solid tumor) criteria. Radiolabel uptake was measured in terms of maximum voxel, standardized uptake value (SUVmax). Results: Ten women between the ages of 48-83 years old (median 55 years) qualified for study, and have been evaluated for response; 4 continue on TDM1 with treatment durations of 3-27 months.Three were trastuzumab-naïve, while 7 had received trastuzumab-containing chemotherapy 3 wks to 55 mo prior to study entry. HER2 was positive by ImmunoHistoChemistry, IHC (3+) in 5 patients, and by FISH testing in the other 5 (3 were 2+ by IHC; 1 was 1+, and 1 was indeterminate). Complete or partial metabolic response was observed in 5 patients. Median Day 2 SUVmax for 64Cu-DOTA trastuzumab was 9.3 g/ml in responding patients, and 4.6 g/ml in non-responders ( P= 0.03). Progression-free survival was longer for patients with higher SUVmax, with a hazard ratio of 0.73 (95% confidence interval 0.46-1.16) for each 1 unit increase in SUVmax. This was not statistically significant, although we can select a threshold SUVmaxfor which the effect is significant even for this small study. Further data is required to confirm such a threshold effect. Conclusions: 64Cu-DOTA-trastuzumab PET imaging predicts benefit from TDM1 in women with biopsy-confirmed HER2+ metastatic disease. Supported by NCI Clinical trial information: NCT02827877.