Department of Medical Oncology, Humanitas Gavazzeni, Bergamo, Italy.
Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy; Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy.
Breast. 2024 Feb;73:103672. doi: 10.1016/j.breast.2024.103672. Epub 2024 Jan 19.
To provide evidence explaining the poor association between pCR and patients' long-term outcome at trial-level in neoadjuvant RCTs for breast cancer (BC), we performed a systematic-review and meta-analysis of all RCTs testing neoadjuvant treatments for early-BC and reporting the hazard ratio of DFS (HR) for the intervention versus control arm stratified by pathological response type (i.e., pCR yes versus no).
The objective was to explore differences of treatment effects on DFS across patients with and without pCR. We calculated the pooled HR in the two strata of pathological response (i.e., pCR yes versus no) using a random-effects model, and assessed the difference between these two estimates using an interaction test.
Ten RCTs and 8496 patients were included in the analysis. Patients obtaining pCR in the intervention-arm had a higher, although not statistically significant, risk of DFS-event as compared with patients obtaining pCR in the control-arm: the pooled HR for the experimental versus control arm was 1.23 (95%CI, 0.91-1.65). On the opposite, the risk of DFS-event was higher for control as compared with the intervention-arm in the stratum of patients without pCR: the pooled HR was 0.86 (95%CI, 0.78-0.95). Treatment effect on DFS was significantly different according to pathological response type (interaction test p: 0.014).
We reported new evidence that contributes to explaining the poor surrogacy value of pCR at trial-level in neoadjuvant RCTs for early-BC.
为了解释在乳腺癌（BC）新辅助 RCT 中，病理完全缓解（pCR）与患者长期结局之间关联较差的原因，我们对所有检测新辅助治疗早期 BC 并报告干预组与对照组之间无病生存期（DFS）风险比（HR）的 RCT 进行了系统评价和荟萃分析，该 HR 按病理反应类型分层（即 pCR 阳性与阴性）。
目的是探索在有无 pCR 的患者中，DFS 治疗效果的差异。我们使用随机效应模型计算了病理反应（即 pCR 阳性与阴性）两个亚组的汇总 HR，并使用交互检验评估这两个估计值之间的差异。
纳入了 10 项 RCT 和 8496 名患者。与对照组相比，在干预组中获得 pCR 的患者发生 DFS 事件的风险更高，但无统计学意义：实验组与对照组的 HR 为 1.23（95%CI，0.91-1.65）。相反，在无 pCR 的患者亚组中，对照组的 DFS 事件风险高于干预组：HR 为 0.86（95%CI，0.78-0.95）。DFS 的治疗效果根据病理反应类型而显著不同（交互检验 p：0.014）。
我们提供了新的证据，有助于解释新辅助 RCT 中早期 BC 患者 pCR 在试验水平上替代价值较差的原因。
