EA1131 study discussant, Melinda Telli, MD, Associate Professor of Medicine at Stanford University, Director of the Breast Cancer Program at the Stanford Cancer Institute, and Associate Director of the Stanford Women’s Cancer Center, commented: “At this point, capecitabine remains preferred as postneoadjuvant therapy in early triple-negative breast cancer.” 1
“Important data have challenged our historical approach to the neoadjuvant treatment of high-risk breast cancer,” she continued. “We have learned [from CREATE-X] that there’s an opportunity to intervene in cases where complete response is not achieved.” EA1131 asked whether platinum agents could improve invasive disease–free survival, specifically in the basal intrinsic subtype,2 she said.
Melinda Telli, MD
“EA1131 was unable to demonstrate noninferiority or superiority of the platinum, so the trial was stopped early for futility after 308 patients with a basal subtype were enrolled. In this group, the 3-year invasive disease–free survival was 42% with platinum and 40% with capecitabine. Although patients with nonbasal triple-negative breast cancer fared somewhat better, the overall outcomes of patients in this trial were poor,” Dr. Telli noted.
Study Strengths and Weaknesses
Dr. Telli saw both strengths and weaknesses in the EA1131 study. “In terms of strengths, the study evaluated an important question in clinical practice, and stopping rules for futility were preplanned. For weaknesses, this study underestimated the impact of excluding patients with smaller tumors that had less percentage of invasive cellularity, and the result was a really high-risk group of patients. There was also some asymmetry in the duration of adjuvant therapy, and the analysis did not consider the variable in the time to adjuvant therapy initiation,” she pointed out.
‘We Need to Build on Our Success’
In addition, Dr. Telli stressed that further studies in this setting are urgently needed to improve outcomes for this high-risk group of patients. It is possible that novel strategies, such as circulating tumor cell DNA, may help guide the use of adjuvant therapy in future postneoadjuvant trials, she indicated.
“We are certainly making progress in terms of optimizing treatment in patients with residual disease, but we need to build on our success—to continue to ask important questions, critically evaluate data, and consider toxicity and the patient’s experience, always,” Dr. Telli concluded.
DISCLOSURE: Dr. Telli has served as a consultant or advisor to AbbVie, Blueprint Medicines, Celgene, Daiichi Sankyo, G1 Therapeutics, Genentech/Roche, Immunomedics, Lilly, Merck, Natera, OncoSec Medical, and Pfizer; has received institutional research funding from AbbVie, Bayer, Biothera, Calithera Biosciences, EMD Serono, Genentech, Medivation, Novartis, OncoSec, Pfizer, PharmaMar, Tesaro, and Vertex; and has held other relationships with G1 Therapeutics and Immunomedics.
REFERENCES
1. Mayer IA, Zhao F, Arteaga CL, et al: A randomized phase III post-operative trial of platinum-based chemotherapy versus capecitabine in patients with residual triple-negative breast cancer following neoadjuvant chemotherapy: ECOG-ACRIN EA1131. 2021 ASCO Annual Meeting. Abstract 605. Presented June 6, 2021.
2. Masuda N, Lee SJ, Ohtani S, et al: Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med 376:2147-2159, 2017.
