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Background <p>The addition of pembrolizumab (KN522) to neoadjuvant doxorubicin, cyclophosphamide (AC), carboplatin and paclitaxel (TC) has significantly improved survival, albeit with increased toxicity. This study aims to evaluate the effectiveness and toxicity of KN522 and to decouple the relative contributions of germline BRCA mutations (gBRCAmut) and pembrolizumab addition.</p> Methods <p>A retrospective analysis of patients with stage II–III triple negative breast cancer, treated at a single tertiary medical center with either KN522 or ACTC.</p> Results <p>Among 127 patients, four cohorts were evaluated: (1) KN522-gBRCAmut (<i>n</i> = 26), (2) KN522-BRCA wildtype (<i>n</i> = 53), (3) ACTC-gBRCAmut (<i>n</i> = 18), (4) ACTC-BRCA wildtype (<i>n</i> = 30). The KN522-gBRCAmut cohort achieved a remarkable pCR rate of 92.3%, compared to 60.4%, 55.6% and 36.7% in cohorts (2), (3) and (4) respectively. Multivariable analysis identified the KN522 protocol (OR 3.69, 95% CI 1.66–8.20; <i>p</i> = 0.001) and gBRCAmut status (OR 3.78, 95% CI 1.57–9.12; <i>p</i> = 0.003) as independent predictors of pCR. Achieving pCR was associated with improved event-free and overall survival (OS) in univariate analyses. In multivariable models, however, pCR remained a significant independent predictor of OS only (HR = 0.15, 95% CI: 0.03–0.72, <i>p</i> = 0.018). KN522 was associated with higher hospitalization rates (40.5% vs. 14.6%, <i>p</i> = 0.003) and more neutropenic fever (NF) events (32.9% vs. 2.1%, <i>p</i> &lt; 0.001), likely due to lower G-CSF prophylaxis during the AC part of the KN522 protocol (21.5% vs. 68.8%, <i>p</i> &lt; 0.001).</p> Conclusions <p>In this analysis, gBRCAmut carriers treated with KN522 achieved remarkably high pCR rates. The observed 40% hospitalizations, primarily due to NF, highlights the need for supportive care optimization, including G-CSF consideration.</p>

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Efficacy and toxicity of neoadjuvant chemotherapy versus chemo-immunotherapy in triple-negative breast cancer patients with and without germline BRCA mutations

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月22日

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  • Tal Etan,
  • Lior Cohen,
  • Yael Bar,
  • Yasmin Leshem,
  • Shir Lerner,
  • Irina Stepansky,
  • Iris Shiran,
  • Amir Sonnenblick,
  • Shlomit Strulov Shachar

摘要

Background

The addition of pembrolizumab (KN522) to neoadjuvant doxorubicin, cyclophosphamide (AC), carboplatin and paclitaxel (TC) has significantly improved survival, albeit with increased toxicity. This study aims to evaluate the effectiveness and toxicity of KN522 and to decouple the relative contributions of germline BRCA mutations (gBRCAmut) and pembrolizumab addition.

Methods

A retrospective analysis of patients with stage II–III triple negative breast cancer, treated at a single tertiary medical center with either KN522 or ACTC.

Results

Among 127 patients, four cohorts were evaluated: (1) KN522-gBRCAmut (n = 26), (2) KN522-BRCA wildtype (n = 53), (3) ACTC-gBRCAmut (n = 18), (4) ACTC-BRCA wildtype (n = 30). The KN522-gBRCAmut cohort achieved a remarkable pCR rate of 92.3%, compared to 60.4%, 55.6% and 36.7% in cohorts (2), (3) and (4) respectively. Multivariable analysis identified the KN522 protocol (OR 3.69, 95% CI 1.66–8.20; p = 0.001) and gBRCAmut status (OR 3.78, 95% CI 1.57–9.12; p = 0.003) as independent predictors of pCR. Achieving pCR was associated with improved event-free and overall survival (OS) in univariate analyses. In multivariable models, however, pCR remained a significant independent predictor of OS only (HR = 0.15, 95% CI: 0.03–0.72, p = 0.018). KN522 was associated with higher hospitalization rates (40.5% vs. 14.6%, p = 0.003) and more neutropenic fever (NF) events (32.9% vs. 2.1%, p < 0.001), likely due to lower G-CSF prophylaxis during the AC part of the KN522 protocol (21.5% vs. 68.8%, p < 0.001).

Conclusions

In this analysis, gBRCAmut carriers treated with KN522 achieved remarkably high pCR rates. The observed 40% hospitalizations, primarily due to NF, highlights the need for supportive care optimization, including G-CSF consideration.