Abstract
144
Objectives: 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).
