Use of 64Cu-DOTA-Trastuzumab PET to Predict Response and Outcome of Patients Receiving Trastuzumab Emtansine for Metastatic Breast Cancer: A Pilot Study.

Joanne E Mortimer,Mary I Carroll,David M Colcher,Nikita Gidwaney,Jinha M Park,Yuan Yuan,Erasmus K Poku,John E Shively,James R Bading,Paul H Frankel,Lusine Tumyan

doi:10.2967/jnumed.121.262940

Abstract

We hypothesized that functional imaging with 64Cu-DOTA-trastuzumab PET/CT would predict the response to the antibody-drug conjugate trastuzumab-emtansine (T-DM1). Methods: Ten women with metastatic human epidermal growth factor receptor 2-positive breast cancer underwent 18F-FDG PET/CT and 64Cu-DOTA-trastuzumab PET/CT on days 1 and 2 before treatment with T-DM1. Results: T-DM1-responsive patients had higher uptake than nonresponsive patients. Day 1 minimum SUVmax (5.6 vs. 2.8, P < 0.02), day 2 minimum SUVmax (8.1 vs. 3.2, P < 0.01), and day 2 average SUVmax (8.5 vs. 5.4, P < 0.05) for 64Cu-DOTA-trastuzumab all favored responding patients. Tumor-level response suggested threshold dependence on SUVmax Patients with a day 2 minimum SUVmax above versus below the threshold had a median time to treatment failure of 28 mo versus 2 mo (P < 0.02). Conclusion: Measurement of trastuzumab uptake in tumors via PET/CT is promising for identifying patients with metastatic breast cancer who will benefit from T-DM1.

Highlights

Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in 15-20% of breast cancers and determines candidacy for trastuzumab which improves disease outcome for all stages of HER2-positive breast cancer [1,2,3].We have used 64Cu-DOTA-trastuzumab PET/CT to study women with recurrent/metastatic breast cancer (4) and reported a positive correlation between tumor uptake of 64Cu-DOTAtrastuzumab and HER2 status as measured by IHC [4, 5]
We report the results of a pilot study testing whether pretreatment 64Cu-DOTA-trastuzumab PET/CT can predict benefit from T-DM1 for HER2-positive metastatic breast cancer
We demonstrated a significant association between tumor uptake of 64Cu-DOTA-trastuzumab and patient benefit from treatment with T-DM1

Summary

Introduction

Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in 15-20% of breast cancers and determines candidacy for trastuzumab which improves disease outcome for all stages of HER2-positive breast cancer [1,2,3]. We have used 64Cu-DOTA-trastuzumab PET/CT to study women with recurrent/metastatic breast cancer (4) and reported a positive correlation between tumor uptake of 64Cu-DOTAtrastuzumab and HER2 status as measured by IHC [4, 5]. Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate that uses trastuzumab to target HER2-positive breast cancer and deliver its cytotoxic payload, DM1 [6]. T-DM1’s mechanism of action and use as a single agent are advantageous for correlating trastuzumab imaging with treatment response. We report the results of a pilot study testing whether pretreatment 64Cu-DOTA-trastuzumab PET/CT can predict benefit from T-DM1 for HER2-positive metastatic breast cancer

Methods

Results

Conclusion