(026) Characterization of Dose-dense Doxorubicin and Cyclophosphamide within the Keynote-522 Trial Regimen for Triple Negative Breast Cancer

Poster Abstract: Background
The Keynote-522 trial established a widely used treatment regimen for triple negative breast cancer (TNBC) with pembrolizumab added to neoadjuvant chemotherapy consisting of doxorubicin and cyclophosphamide given every three weeks (classic AC). Although dose-dense AC administered every two weeks is standard of care, there are logistical concerns of desynchrony in combination with pembrolizumab given every three weeks.

Objective
The purpose of this study is to characterize the efficacy, safety, and timing of a modified Keynote-522 regimen including dose-dense AC at Henry Ford Hospital for TNBC.

Methods
This retrospective cohort study will include patients aged 18 years and older with TNBC who received at least two cycles of doxorubicin and cyclophosphamide alongside pembrolizumab as neoadjuvant chemotherapy from October 1, 2021 to December 31, 2023 at Hendry Ford Hospital. Patient characteristics to be collected include age, gender, menopausal status, ECOG performance status, tumor classification, nodal involvement, overall cancer stage, HER-2 status score, PD-L1 expression, and Ki67 expression. The primary endpoint will be incidence of grade 4 neutropenia using Common Terminology Criteria for Adverse Events Version 5.0. Secondary endpoints include pathologic complete response rate at time of surgery, incidence of adverse events including anemia and immunotherapy-related toxicity, incidence of treatment delays, incidence of switching from dose-dense AC to classic or vice versa, sequence of neoadjuvant phases, total length of treatment, number of infusion center visits, number of hospital admissions, and number of lab visits. With an estimated enrollment ratio of dose-dense to classic AC of 5:1, 72 participants are needed to yield 80% power in detecting a difference in the primary outcome between treatment groups.

Results
Research is in progress.

Conclusions
Research is in progress.

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2. National Comprehensive Cancer Network. Breast Cancer. (Version 4.2023) https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed September 5, 2023.
3. Citron ML, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: First report of intergroup trial C9741/cancer and leukemia group B trial 9741. J Clin Oncol 2003;21:1431-1439.
4. Schmid P, et al; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. doi: 10.1056/NEJMoa1910549. PMID: 32101663.