Resident Allegheny Health Network Pittsburgh, Pennsylvania, United States
Poster Abstract:
Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis. Historically, systemic chemotherapy has been the preferred treatment strategy for high-risk early-stage TNBC. Doxorubicin with cyclophosphamide (AC) administered dose-dense (every 2 weeks) is preferred over conventional dosing (every three weeks) due to improved disease-free survival and overall survival. Since the emergence of immunotherapy, practice has evolved to include pembrolizumab as part of first-line therapy for TNBC. The KEYNOTE-522 trial, evaluating neoadjuvant pembrolizumab with standard chemotherapy, including conventional AC, demonstrated improved pathologic complete response (pCR) and event-free survival, yet safety and efficacy of pembrolizumab with dose-dense AC is largely unknown in this setting. This study will evaluate clinical and safety outcomes of AC administered dose-dense versus conventional dosing within the KEYNOTE-522 regimen.
Objectives: The objectives of this study are to compare the rates of pCR (ypT0/Tis ypN0) between patients receiving dose-dense AC versus conventional AC within the KEYNOTE-522 regimen for early-stage TNBC and to evaluate the toxicity of dose-dense AC administered with pembrolizumab.
Methods: This study is a retrospective chart review of patients with newly diagnosed, early-stage TNBC receiving neoadjuvant treatment with the KEYNOTE-522 regimen including AC administered dose-dense or conventionally. All patients were treated within Allegheny Health Network between 8/1/21 – 12/1/23 and received at least one dose of pembrolizumab. Patients were excluded if they had metastatic disease, a local recurrence, or required steroids greater than 10 mg of prednisone per day. Electronic health records will be reviewed for baseline characteristics, tumor staging at diagnosis, surgical outcomes, and safety endpoints. The primary objective of pathological complete response at surgery will be analyzed by Chi squared tests and secondary safety endpoints will be evaluated by descriptive statistics.
Results: Results will be analyzed to compare efficacy and safety outcomes between dose-dense AC and conventional AC within the KEYNOTE-522 regimen.
Conclusions: It is anticipated that this project will provide insight into the safety and efficacy of dose-dense AC within the KEYNOTE-522 regimen and guide prescribing patterns for optimal use of AC with pembrolizumab for early-stage TNBC.
References (must also be included in final poster): 1. Huang M, O'Shaughnessy J, Zhao J, et al. Evaluation of Pathologic Complete Response as a Surrogate for Long-Term Survival Outcomes in Triple-Negative Breast Cancer. J Natl Compr Canc Netw. 2020;18(8):1096-1104. doi:10.6004/jnccn.2020.7550
2. Citron ML, Berry DA, Cirrincione C, 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 [published correction appears in J Clin Oncol. 2003 Jun 1;21(11):2226]. J Clin Oncol. 2003;21(8):1431-1439. doi:10.1200/JCO.2003.09.081
3. Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020;382(9):810-821. doi:10.1056/NEJMoa1910549
4. Masuda N, Lee SJ, Ohtani S, et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 2017;376(22):2147-2159. doi:10.1056/NEJMoa1612645
5. Olivia W et al. Assessment of efficacy and safety of dose-dense doxorubicin and cyclophosphamide (ddAC) in combination with pembrolizumab in early-stage, triple-negative breast cancer.Journal of Clinical Oncology 2023 41:16_suppl, e12618-e12618
