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

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