Abstract PD4-12: Use of 64Cu-DOTA-trastuzumab positron emission tomography (PET) to predict response to ado-trastuzumab emtansine (TDM1)

Background: We have demonstrated that 64Cu-DOTA trastuzumab is an effective PET imaging agent for HER2 positive breast cancer and are now seeking to evaluate the methodology for prediction of response and benefit to ado-trastuzumab emtansine (TDM1) in women with metastatic disease. Methods: Patients with metastatic breast cancer were eligible if they had biopsy confirmed HER2 + disease, at least 1 site of metastasis 2.0 cm or larger outside the biopsy site, and were to receive TDM1 as therapy. Pretreatment staging included 18F-FDG/PET. Prior to injection of 64Cu-DOTA-trastuzumab, patients received 45 mg of cold trastuzumab to reduce liver uptake. PET-CT scans were obtained at 21-25 h and 47-48 h over fields of view chosen in reference to 18F-FDG scans. TDM1 was administered at a dose of 3.6 mg/kg every 3 weeks. Restaging 18F-FDG/PET was performed every 2 cycles, and response to therapy was determined by PERCIST criteria. The radiolabel uptake was measured in terms of maximum voxel standardized uptake value (SUVmax). Results: Ten women enrolled on study and are evaluable for response; three continue on TDM1 for 22-40 months and four patients remained on treatment for at least 1 year. The median age was 54.5 years (48-83 years); seven received prior trastuzumab-containing chemotherapy 3 wks to 55 months prior to study entry. HER2 was positive by IHC in 5 and by FISH in 5 (3 were 2+ by IHC; 1 was 1+ and 1 indeterminate). Complete or partial metabolic response was observed in 5 patients. Patients had their average SUVmax on 64Cu-DOTA trastuzumab PET (aSUVmax) assessed in addition to individual assessments on up to 8 lesions on both Day1 and Day2. The mean aSUVmax was (6.3, 8.8) for responding patients and (4.4, 5.2) for non-responder (day1, day2). The difference between responders and non-responders on Day1 aSUVmax was marginally significant (p=0.06), but significant on Day2 (p=0.04). The three highest aSUVmax on both day1 and day2 were three of the four patients with PFS>1 year. Data on the relationship of 64Cu-DOTA trastuzumab PET to IHC and FISH, and individual lesion SUVmax including evidence suggesting a potential threshold effect will be presented. Conclusions: In women with biopsy confirmed HER2 positive metastatic disease, 64Cu-DOTA-trastuzumab PET imaging is predictive for response to TDM1. Citation Format: Mortimer JE, Bading JR, Frankel P, Tumyan L, Tran TT, Rockne RC, Shively JE, Gidwaney N, Park J, Colcher DM. Use of 64Cu-DOTA-trastuzumab positron emission tomography (PET) to predict response to ado-trastuzumab emtansine (TDM1) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD4-12.