Detrimental Impact of Chemotherapy Dose Reduction or Discontinuation in Early Stage Triple-Negative Breast Cancer Treated With Pembrolizumab and Neoadjuvant Chemotherapy: A Multicenter Experience

IF 2.9 3区医学 Q2 ONCOLOGY

Clinical breast cancer Pub Date : 2024-08-06 DOI:10.1016/j.clbc.2024.08.005

Jayasree Krishnan , Archit Patel , Arya Mariam Roy , Malak Alharbi , Ankita Kapoor , Song Yao , Thaer Khoury , Chi-Chen Hong , Nicole Held , Anumita Chakraborty , Pawel Kaliniski , Ahmed Salman , Kayla Catalfamo , Kristopher Attwood , Vatsala Kirtani , Saba S. Shaikh , Lubna N. Chaudhary , Shipra Gandhi

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引用次数: 0

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.

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在使用 Pembrolizumab 和新辅助化疗的早期三阴性乳腺癌患者中减少化疗剂量或停止化疗的不利影响：多中心经验。

研究背景基于Keynote-522（KN-522）临床试验中较高的无事件生存率和病理完全反应（pCR），Pembrolizumab联合新辅助化疗（NAC）是目前治疗早期三阴性乳腺癌（TNBC）的标准方案。然而，这种积极的五药方案与免疫相关不良事件（irAEs）的风险增加有关。我们研究了该方案的实际临床结果和毒性，以及预测 pCR 和 irAEs 的因素：我们确定并摘录了2021年7月1日至2023年12月31日期间在美国4家学术机构接受KN-522方案治疗的153例早期TNBC患者的数据，进行了描述性分析，并进行了单变量和多变量分析，以确定与pCR和irAEs相关的因素：中位年龄为52岁（四分位间范围为42-60岁），66%为白人，24%为黑人，患者均为I/II期（67%）、结节阴性疾病（58%）、3级肿瘤（86%），合并症≥1种（68%）。约21%的患者因毒性而停用pembrolizumab；50%的患者接受了相对剂量强度（RDI）更低的化疗（减量或停药）。在153例患者中，99例（64.7%）获得了pCR，83例（54%）出现了irAE，其中18例（12%）≥3级irAE。大多数（90%）虹膜AE发生在新辅助治疗阶段。在多变量分析中，I/II期与III期疾病（OR 1.55，CI 1.04-2.33，P = .03）、年龄（OR 0.96，CI 0.93-0.99，P = .01）以及NAC完全RDI与减少RDI（OR 1.53，CI 1.04-2.26，P = .03）与较高的pCR率相关。较少的彭博利珠单抗周期与较高的irAEs可能性相关（OR 1.52，CI 1.07-2.16，P = .02），这可能是因为出现irAEs的患者较早停药并接受了少于8个周期的彭博利珠单抗治疗：我们的研究验证了KN-522方案的临床疗效；然而，我们观察到，在这一真实世界人群中，irAEs的发生率较高（54%）。较低的分期和较年轻的年龄与获得 pCR 的可能性较高有关。据观察，与毒性相关的化疗剂量减少或中止会对获得 pCR 的可能性产生不利影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical breast cancer 医学-肿瘤学

CiteScore

5.40

自引率

3.20%

发文量

174

审稿时长

48 days

期刊介绍： Clinical Breast Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of breast cancer. Clinical Breast Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of breast cancer. The main emphasis is on recent scientific developments in all areas related to breast cancer. Specific areas of interest include clinical research reports from various therapeutic modalities, cancer genetics, drug sensitivity and resistance, novel imaging, tumor genomics, biomarkers, and chemoprevention strategies.