Go Back   HER2 Support Group Forums > Breast Cancer Meeting Highlights
Register Gallery FAQ Members List Calendar Search Today's Posts Mark Forums Read

Breast Cancer Meeting Highlights News fro recent ASCO and San Antonio Meetings

Thread Tools Display Modes
Old 06-05-2019, 08:10 AM   #1
Senior Member
Join Date: Nov 2005
Posts: 349
HER2 heterogeneity as a predictor of response to neoadjuvant T-DM1 plus pertuzumab


HER2 heterogeneity as a predictor of response to neoadjuvant T-DM1 plus pertuzumab: Results from a prospective clinical trial.

Adjuvant Therapy

Breast Cancer—Local/Regional/Adjuvant

2019 ASCO Annual Meeting

Abstract No:

J Clin Oncol 37, 2019 (suppl; abstr 502)

Author(s): Otto Metzger Filho, Giuseppe Viale, Lorenzo Trippa, Tianyu Li, Denise A. Yardley, Ingrid A. Mayer, Vandana Gupta Abramson, Carlos L. Arteaga, Laura Spring, Adrienne Gropper Waks, Michalina Janiszewska, Eileen Wrabel, Michelle Demeo, Aditya Bardia, Tari A. King, Kornelia Polyak, Eric P. Winer, Ian E. Krop; Dana-Farber Cancer Institute, Boston, MA; Division of Pathology, European Institute of Oncology, IRCCS, Milan, Italy; Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA; Dana Farber Cancer Institute, Boston, MA; Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Vanderbilt-Ingram Cancer Center, Nashville, TN; Vanderbilt University Ingram Cancer Center, Nashville, TN; Massachusetts General Hospital, Boston, MA; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA; Breast Oncology Program, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA

Abstract Disclosures

Background: HER2 targeted therapy without chemotherapy may be insufficient to completely eradicate a HER2+ cancer in cases of significant intratumor HER2 heterogeneity (ITH-HER2). Methods: We conducted a single-arm phase II study enrolling centrally confirmed HER2+ breast cancer. Pts received 6 cycles of T-DM1 plus Pertuzumab before surgery. Central ITH-HER2 was assessed on baseline ultrasound-guided core biopsies from 2 distinct areas of each tumor (3 cores/site). ITH-HER2 was defined as at least one of the six areas demonstrating either 1) HER2 positivity by FISH in > 5% and < 50% of tumor cells (i.e., CAP guideline) or 2) an area of tumor that tested HER2 negative. The primary objective is the association between pathologic complete response (pCR) and ITH, stratified by ER status. pCR defined as residual cancer burden (RCB) 0. Results: 164 pts with centrally confirmed HER2+ tumors were enrolled from 1/2015 to 1/2018. 2 pts withdrew consent. Median tumor size by imaging was 2.8 cm (IQR 2.1-3.8cm); 111 (69%) were ER+ and 51 (32%) ER-. 8 pts discontinued tx (6 due to disease progression, 2 due to toxicity). 49% of pts had a pCR (RCB-0), 14% RCB-I, 26% RCB-II and 11% RCB-III. Higher rates of RCB-0 were seen in ER- (65%) versus ER+ (42%). ITH-HER2 was detected in 10% (16/157) of evaluable cases. No pCR was observed among cases classified as heterogeneous (RCB-I 25%, RCB-II 25%, RCB-III 50%). The study met its primary endpoint by demonstrating a significant association between ITH-HER2 and pCR stratified by ER status (p < .0001). Secondary analysis also demonstrated a significant association between ITH-HER2 and pathologic response defined as RCB 0 or I (OR = 5.6, p = 0.004). Exploratory analysis revealed higher rates of RCB-0 among tumors centrally classified as HER2 3+ (56% [66/118]) versus HER2 2+ (27% [10/37]), (OR = 3.4, p = 0.002). The association of ITH-HER2 and pCR was maintained when stratifying by ER status and HER2 IHC (2+ vs. 3+), (p = 0.002). Conclusions: ITH-HER2 assessed by routine pathology evaluation is a strong predictor of pCR to a dual-HER2 targeted therapy regimen. If validated, ITH-HER2 may need to be considered in selection of pts for HER2-targeted regimens without chemotherapy in the curative setting. Clinical trial information: NCT02326974
Nguyen is offline   Reply With Quote

Thread Tools
Display Modes

Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

BB code is On
Smilies are On
[IMG] code is On
HTML code is On

Forum Jump

All times are GMT -7. The time now is 12:07 AM.

Powered by vBulletin® Version 3.8.7
Copyright ©2000 - 2021, vBulletin Solutions, Inc.
Copyright HER2 Support Group 2007 - 2021
free webpage hit counter