Pathologic and molecular responses to neoadjuvant trastuzumab and/or lapatinib from a phase II randomized trial in HER2-positive breast cancer (TRIO-US B07)
Abstract
In this multicenter, open-label, randomized phase II investigator-sponsored neoadjuvant trial with funding provided by Sanofi and GlaxoSmithKline (TRIO-US B07, Clinical Trials NCT00769470), participants with early-stage HER2-positive breast cancer (N = 128) were recruited from 13 United States oncology centers throughout the Translational Research in Oncology network. Participants were randomized to receive trastuzumab (T; N = 34), lapatinib (L; N = 36), or both (TL; N = 58) as HER2-targeted therapy, with each participant given one cycle of this designated anti-HER2 therapy alone followed by six cycles of standard combination chemotherapy with the same anti-HER2 therapy. The primary objective was to estimate the rate of pathologic complete response (pCR) at the time of surgery in each of the three arms. In the intent-to-treat population, we observed similar pCR rates between T (47%, 95% confidence interval [CI] 30–65%) and TL (52%, 95% CI 38–65%), and a lower pCR rate with L (25%, 95% CI 13–43%). In the T arm, 100% of participants completed all protocol-specified treatment prior to surgery, as compared to 69% in the L arm and 74% in the TL arm. Tumor or tumor bed tissue was collected whenever possible pre-treatment (N = 110), after one cycle of HER2-targeted therapy alone (N = 89), and at time of surgery (N = 59). Higher-level amplification of HER2 and hormone receptor (HR)-negative status were associated with a higher pCR rate. Large shifts in the tumor, immune, and stromal gene expression occurred after one cycle of HER2-targeted therapy. In contrast to pCR rates, the L-containing arms exhibited greater proliferation reduction than T at this timepoint. Immune expression signatures increased in all arms after one cycle of HER2-targeted therapy, decreasing again by the time of surgery. Our results inform approaches to early assessment of sensitivity to anti-HER2 therapy and shed light on the role of the immune microenvironment in response to HER2-targeted agents.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 17, 2020
- Source ID
- 10.1038/s41467-020-19494-2
Entities
People
- Alejandra Perez
- April Kennedy
- Armando Giuliano
- Aruna Mani
- Brad Adams
- Brian Dicarlo
- Carmen Calfa
- Christina Curtis
- David Molthrop
- Dennis J. Slamon
- Eran Kotler
- Gregory R Bean
- Heather Allen
- Hsiao-wang Chen
- Jason J. Zoeller
- Jennifer L Caswell
- Joan Brugge
- Judy Dering
- Katherine Pogrebniak
- Lee Zehngebot
- Linda Bosserman
- Michael F. Press
- Ravindranath Patel
- Robert Dichmann
- Sara A. Hurvitz
Organizations
- National Cancer Institute
- The Breast Cancer Research Foundation
- United States Department of Defense