Detrimental Impact of Chemotherapy Dose Reduction or Discontinuation in Early Stage Triple-Negative Breast Cancer Treated With Pembrolizumab and Neoadjuvant Chemotherapy: A Multicenter Experience
Department
Oncology and Hematology
Document Type
Article
Publication Title
Clinical Breast Cancer
Abstract
Background: Pembrolizumab combined with neoadjuvant chemotherapy (NAC) is the current standard of care in early stage triple-negative breast cancer (TNBC) based on higher event-free survival and pathological complete response (pCR) in Keynote-522 (KN-522) clinical trial. However, this aggressive five-drug regimen is associated with increased risks for immune-related adverse events (irAEs). We investigated real-world clinical outcomes and toxicity of this regimen as well as factors predictive of pCR and irAEs.
Methods: We identified and abstracted data from 153 early-stage TNBC patients treated with the KN-522 regimen between July 1, 2021, and December 31, 2023, at 4 academic institutions in the U.S. Descriptive analysis was conducted, univariate and multivariate analyses were performed to identify factors associated with pCR and irAEs.
Results: The median age was 52 years (interquartile range, 42-60years), with 66% White and 24% Black patients with stage I/II (67%), node-negative disease (58%), grade 3 (86%) tumors, and ≥ 1 comorbidities (68%). Approximately 21% discontinued pembrolizumab, because of toxicity; ∼50% received a lower relative dose intensity (RDI) of chemotherapy (dose reduction or discontinuation). Of the 153 patients, 99 (64.7%) achieved pCR and 83 (54%) experienced an irAE, with 18 (12%) having ≥ grade 3 irAE. The majority (90%) of the irAEs were observed during neoadjuvant phase. Stage I/II versus stage III disease (OR 1.55, CI 1.04-2.33, P = .03), age (OR 0.96, CI 0.93-0.99, P = .01) and full versus reduced RDI of NAC (OR 1.53, CI 1.04-2.26, P = .03) were associated with higher pCR rates on multivariate analyses. Fewer cycles of pembrolizumab were associated with a higher likelihood of irAEs (OR 1.52, CI 1.07-2.16, P = .02), likely explained by the early discontinuation and receipt of less than 8 cycles of pembrolizumab in patients who experienced irAEs.
Conclusions: Our study validates the clinical efficacy of KN-522 regimen; however, we observed a higher incidence of irAEs (54%) in this real-world population. Lower stage and younger age were associated with higher likelihood of achieving pCR. Toxicity-related chemotherapy dose reduction or discontinuation was observed to adversely impact the likelihood of achieving pCR.
First Page
e701
Last Page
e711.e2
DOI
10.1016/j.clbc.2024.08.005
Volume
24
Issue
8
Publication Date
12-1-2024
Medical Subject Headings
Humans; Triple Negative Breast Neoplasms (drug therapy, pathology); Female; Middle Aged; Neoadjuvant Therapy (adverse effects, methods); Adult; Antibodies, Monoclonal, Humanized (adverse effects, administration & dosage); Antineoplastic Combined Chemotherapy Protocols (therapeutic use, adverse effects); Neoplasm Staging; Retrospective Studies; Antineoplastic Agents, Immunological (adverse effects, administration & dosage, therapeutic use); Chemotherapy, Adjuvant (adverse effects, methods)
PubMed ID
39198116
Recommended Citation
Krishnan, J., Patel, A., Roy, A. M., Alharbi, M., Kapoor, A., Yao, S., Khoury, T., Hong, C., Held, N., Chakraborty, A., Kaliniski, P., Salman, A., Catalfamo, K., Attwood, K., Kirtani, V., Shaikh, S. S., Chaudhary, L. N., & Gandhi, S. (2024). Detrimental Impact of Chemotherapy Dose Reduction or Discontinuation in Early Stage Triple-Negative Breast Cancer Treated With Pembrolizumab and Neoadjuvant Chemotherapy: A Multicenter Experience. Clinical Breast Cancer, 24 (8), e701-e711.e2. https://doi.org/10.1016/j.clbc.2024.08.005