Khoury Thaer, Gandhi Shipra, Tozbikian Gary, Fadare Oluwole, Syed Samira, To Briana, Quiroga Dionisia, Yao Song, Attwood Kristopher, Yu Han, Fang Yisheng
Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States.
Department of Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States.
Oncologist. 2025 Sep 1;30(9). doi: 10.1093/oncolo/oyaf231.
Our objective is to compare the response rate between two matched cohorts of early-stage TNBC (chemotherapy: CT + immune checkpoint inhibitor: ICI vs CT alone) and to define clinicopathological variables to identify a subgroup of patients who could be spared or benefit from ICI.
Patients treated with CT + ICI according to KEYNOTE-522 (KN-522) (n = 128) were included in the study and matched 1:1 with patients treated with CT alone. Matching criteria included age range (10 years), race, clinical stage (c)-AJCC, and histological type (metaplastic [MpBC] vs no special type [IC-NST]). The following histological characteristics in the core needle biopsy (CNB) were included: histological type, Nottingham grade, degree of necrosis, and percentage of tumor-infiltrating lymphocytes (TILs). The residual cancer burden (RCB) was categorized into 0 (pCR), I, II, or III. To identify a subgroup of patients who could be spared or benefit from adding ICI, an analysis of the penalized maximum likelihood estimate was performed.
pCR was achieved in 50% of patients treated with CT + ICI vs 35.9% treated with CT alone (P = .02). In the CT group, lower TILs in CNB, non-Black race, MpBC histology, and a higher degree of necrosis were associated with non-pCR. Patients were categorized into quartiles (Q) based on the predicted risk of non-pCR to CT (Q1 represents the lowest risk and Q4 represents the highest risk of non-pCR). In Q4, the pCR rate with CT alone was only 2.9% (1/46) vs 20% (6/64) in the CT + IT cohort (P = .044). The following variables were associated with Q4 vs Q1-3: non-Black race (96.9% vs 88%, P = .04), MpBC histology (29.7% vs 1.6%, P < .01), lymph node positive disease (54.6% vs 50%, P < .01), Nottingham grade 2 (32.8% vs 6.3%, P < .01), and lower mean TILs (12.8 ± 15 vs 36.7 ± 26.5, P < .01).
The efficacy of CT + ICI regimen in the real world, although higher than CT, is lower than that observed on the KN 522 clinical trial. Our results need validation in a larger cohort.
我们的目标是比较两组匹配的早期三阴性乳腺癌队列（化疗：CT + 免疫检查点抑制剂：ICI 与单纯 CT）的缓解率，并确定临床病理变量，以识别可以避免使用或从 ICI 中获益的患者亚组。
根据 KEYNOTE-522（KN-522）接受 CT + ICI 治疗的患者（n = 128）纳入本研究，并与单纯接受 CT 治疗的患者进行 1:1 匹配。匹配标准包括年龄范围（10 岁）、种族、临床分期（c）-AJCC 和组织学类型（化生性 [MpBC] 与非特殊类型 [IC-NST]）。包括以下在粗针活检（CNB）中的组织学特征：组织学类型、诺丁汉分级、坏死程度和肿瘤浸润淋巴细胞（TILs）百分比。残余癌负担（RCB）分为 0（pCR）、I、II 或 III 级。为了识别可以避免使用或从添加 ICI 中获益的患者亚组，进行了惩罚最大似然估计分析。
接受 CT + ICI 治疗的患者中有 50% 达到 pCR，而单纯接受 CT 治疗的患者为 35.9%（P = .02）。在 CT 组中，CNB 中较低的 TILs、非黑人种族、MpBC 组织学和较高的坏死程度与非 pCR 相关。根据对 CT 的非 pCR 预测风险将患者分为四分位数（Q）（Q1 代表最低风险，Q4 代表最高非 pCR 风险）。在 Q4 中，单纯 CT 的 pCR 率仅为 2.9%（1/46），而 CT + IT 队列中为 20%（6/64）（P = .044）。以下变量与 Q4 与 Q1-3 相关：非黑人种族（96.9% 对 88%，P = .04）、MpBC 组织学（29.7% 对 1.6%，P < .01）、淋巴结阳性疾病（54.6% 对 50%，P < .01）、诺丁汉 2 级（32.8% 对 6.3%，P < .01）和较低的平均 TILs（12.8 ± 15 对 36.7 ± 26.5，P < .01）。
CT + ICI 方案在现实世界中的疗效虽然高于 CT，但低于在 KN 522 临床试验中观察到的疗效。我们的结果需要在更大的队列中进行验证。
