RT Journal Article
SR Electronic
T1 89Zr-Trastuzumab PET/CT for Prediction of Response to HER2-targeted therapy in Patients with HER2 Mutant Lung Cancer: An Exploratory Phase 2 Trial
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 144
OP 144
VO 60
IS supplement 1
A1 Ulaner, Gary
A1 Offin, Michael
A1 Scaltriti, Maurizio
A1 Myers, Mackenzie
A1 Venkatesh, Aishwarya
A1 Panora, Elizabeth
A1 Kris, Mark
A1 Rudin, Charles
A1 Arcila, Maria
A1 Lyashchenko, Serge
A1 Lewis, Jason
A1 Li, Bob
YR 2019
UL http://jnm.snmjournals.org/content/60/supplement_1/144.abstract
AB 144Objectives: Ado-trastuzumab emtansine (T-DM1) is a HER2 targeted antibody drug conjugate (ADC) that has demonstrated clinical activity in patients with HER2 mutant lung cancers. We hypothesized that the degree of uptake of 89Zr-trastuzumab, a HER2-targeting PET radio-antibody, may serve as a predictor of response to T-DM1. Methods: Patients with metastatic HER2 mutant or amplified cancers were enrolled in a phase 2 trial testing the antitumor activity of T-DM1. Before treatment, an expansion cohort of patients with HER2 mutant lung cancers underwent 89Zr-trastuzumab PET/CT for quantitation of HER2-expression in tumors, as well as FDG PET/CT for baseline RECIST and PERCIST measurements. Patients were treated with T-DM1 at 3.6mg/kg IV every 3 weeks. The primary endpoint was overall response rate (ORR) using PERCIST. Results: A total of 112 patients with HER2 mutant or amplified cancers were enrolled in the trial. The expansion cohort including 89Zr-trastuzumab PET/CT enrolled 12 patients with HER2 mutant lung cancers. ORR in the expansion cohort was 7 of 12 (58%) by PERCIST. Pre-treatment 89Zr-trastuzumab PET/CT demonstrated 89Zr-trastuzumab-avid lesions in 4 patients, and all 4 patients (100%) subsequently responded to T-DM1 treatment. Pre-treatment 89Zr-trastuzumab showed no uptake above mediastinal background in 8 patients, and only 3 of these 8 (37%) responded to TDM1 treatment. Conclusion: This study confirmed the efficacy of T-DM1 in patients with HER2 mutant lung cancers. HER2-targeted imaging with 89Zr-trastuzumab PET/CT may predict response to T-DM1. This pilot expansion cohort is an example of how HER2-targeted PET imaging may help select anti-HER2 therapies in individual patients, a paradigm that could be applicable to a wide range of malignancies with HER2 aberrations. Research support: Conquer Cancer Foundation, Lowenstein Research Fund, Genentech, the Geoffrey Beene Cancer Center at MSKCC and the Comprehensive Cancer Center Core Grant (NIH P30 CA008748).