Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, 39 Jabotinski St., 49100, Petah Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, PO Box 39040, 6997801, Tel Aviv, Israel.
J Cancer Res Clin Oncol. 2021 Nov;147(11):3369-3379. doi: 10.1007/s00432-021-03591-w. Epub 2021 Mar 21.
There is uncertainty regarding the role of adding immune checkpoint inhibitors (ICIs) to neoadjuvant chemotherapy (NACT) in early-stage triple-negative breast cancer (TNBC).
We identified randomized controlled trials (RCTs) comparing ICIs combined with NACT to NACT in early-stage TNBC. Efficacy outcomes included pathological complete response (pCR) and event-free survival (EFS). Toxicity data included any grade 3/4 adverse events (AEs), serious AEs, AEs leading to death, common and meaningful AEs associated with chemotherapy and immune-related AEs. Odds ratio (ORs), hazard ratios (HR) and their respective 95% confidence intervals (CI) for efficacy and toxicity were extracted and pooled in a meta-analysis. Differences in the odds for pCR between programmed death ligand 1 (PD-L1) status and between PD-L1 and PD-1 inhibitors were also assessed.
Five RCTs comprising 2,075 patients were analyzed. Compared to NACT alone, combination of ICIs and NACT significantly improved pCR (OR 1.75, 95% CI 1.25-2.47, p = 0.001) and EFS (HR 0.66, 95% CI 0.48-0.91, p = 0.01). Magnitude of effect on pCR was similar between PD-L1-positive and PD-L1-negative tumors (p for the subgroup difference = 0.80) and between PD-L1 and PD-1 inhibitors (p = 0.27). The combination treatment resulted in higher odds of any grade 3/4 AEs (OR 1.31, p = 0.02) and serious AEs (OR 1.84, p = 0.006), with no statistically significant difference in AEs leading to death (OR 1.67, p = 0.51). Higher magnitude of toxicity was observed for immune-related AEs.
Combination of ICIs and NACT were associated with improved outcome in early-stage TNBC while increasing toxicity significantly. Longer follow-up is desired to better understand the risk and benefit ratio of this combination.
在早期三阴性乳腺癌（TNBC）中，添加免疫检查点抑制剂（ICI）联合新辅助化疗（NACT）的作用尚不确定。
我们确定了比较 ICI 联合 NACT 与 NACT 治疗早期 TNBC 的随机对照试验（RCT）。疗效结局包括病理完全缓解（pCR）和无事件生存（EFS）。毒性数据包括任何 3/4 级不良事件（AE）、严重 AE、导致死亡的 AE、与化疗相关的常见且有意义的 AE 和免疫相关 AE。提取并汇总了疗效和毒性的比值比（OR）、风险比（HR）及其各自的 95%置信区间（CI）。还评估了程序性死亡配体 1（PD-L1）状态和 PD-L1 与 PD-1 抑制剂之间的 pCR 几率差异。
对 2075 名患者进行了五项 RCT 分析。与单独 NACT 相比，ICI 联合 NACT 显著提高了 pCR（OR 1.75，95%CI 1.25-2.47，p=0.001）和 EFS（HR 0.66，95%CI 0.48-0.91，p=0.01）。PD-L1 阳性和 PD-L1 阴性肿瘤之间（亚组差异 p=0.80）和 PD-L1 与 PD-1 抑制剂之间（p=0.27）的 pCR 效应大小相似。联合治疗导致任何 3/4 级 AE 的几率更高（OR 1.31，p=0.02）和严重 AE（OR 1.84，p=0.006），但导致死亡的 AE 几率无统计学差异（OR 1.67，p=0.51）。免疫相关 AE 的毒性更大。
ICI 联合 NACT 可改善早期 TNBC 的疗效，但显著增加毒性。需要更长时间的随访以更好地了解这种联合的风险和获益比。
