West German Study Group, Moenchengladbach, Germany.
Ev. Hospital Bethesda, Breast Center Niederrhein, Moenchengladbach, Germany.
Clin Cancer Res. 2022 Nov 14;28(22):4995-5003. doi: 10.1158/1078-0432.CCR-22-0482.
Although optimal treatment in early triple-negative breast cancer (TNBC) remains unclear, de-escalated chemotherapy appears to be an option in selected patients within this aggressive subtype. Previous studies have identified several pro-immune factors as prognostic markers in TNBC, but their predictive impact regarding different chemotherapy strategies is still controversial.
ADAPT-TN is a randomized neoadjuvant multicenter phase II trial in early patients with TNBC (n = 336) who were randomized to 12 weeks of nab-paclitaxel 125 mg/m2 + gemcitabine or carboplatin d 1,8 q3w. Omission of further (neo-) adjuvant chemotherapy was allowed only in patients with pathological complete response [pCR, primary endpoint (ypT0/is, ypN0)]. Secondary invasive/distant disease-free and overall survival (i/dDFS, OS) and translational research objectives included quantification of a predictive impact of markers regarding selection for chemotherapy de-escalation, measured by gene expression of 119 genes (including PAM50 subtype) by nCounter platform and stromal tumor-infiltrating lymphocytes (sTIL).
After 60 months of median follow-up, 12-week-pCR was favorably associated (HR, 0.24; P = 0.001) with 5y-iDFS of 90.6% versus 62.8%. No survival advantage of carboplatin use was observed, despite a higher pCR rate [HR, 1.04; 95% confidence interval (CI), 0.68-1.59]. Additional anthracycline-containing chemotherapy was not associated with a significant iDFS advantage in pCR patients (HR, 1.29; 95% CI, 0.41-4.02). Beyond pCR rate, nodal status and high sTILs were independently associated with better iDFS, dDFS, and OS by multivariable analysis.
Short de-escalated neoadjuvant taxane/platinum-based combination therapy appears to be a promising strategy in early TNBC for using pCR rate as an early decision point for further therapy (de-) escalation together with node-negative status and high sTILs. See related commentary by Sharma, p. 4840.
尽管早期三阴性乳腺癌（TNBC）的最佳治疗方法仍不清楚，但在这种侵袭性亚型的选定患者中，降级化疗似乎是一种选择。先前的研究已经确定了几个促免疫因素作为 TNBC 的预后标志物，但它们在不同化疗策略方面的预测影响仍存在争议。
ADAPT-TN 是一项早期 TNBC 患者的随机、多中心、Ⅱ期新辅助试验（n=336），这些患者被随机分为 12 周纳武利尤单抗 125mg/m2+吉西他滨或卡铂 d1,8 q3w。仅在病理完全缓解（ypT0/is、ypN0，主要终点）的患者中才允许省略进一步（新）辅助化疗。次要的侵袭性/远处无病生存和总生存（i/dDFS、OS）和转化研究目标包括通过 nCounter 平台测量的 119 个基因（包括 PAM50 亚型）的基因表达来量化标志物对化疗降级选择的预测影响，以及间质肿瘤浸润淋巴细胞（sTIL）。
中位随访 60 个月后，12 周 pCR 与 5 年 iDFS 率为 90.6%（95%CI：83.4-94.6）相关，与 62.8%（95%CI：53.1-70.3）相比，具有显著优势（HR：0.24；P=0.001）。尽管 pCR 率较高，但未观察到卡铂使用的生存优势[HR：1.04；95%CI：0.68-1.59]。在 pCR 患者中，加用蒽环类药物化疗与 iDFS 无显著优势相关（HR：1.29；95%CI：0.41-4.02）。多变量分析显示，除了 pCR 率外，淋巴结状态和高 sTIL 与更好的 iDFS、dDFS 和 OS 独立相关。
早期 TNBC 短时间降级新辅助紫杉醇/铂类联合治疗似乎是一种很有前途的策略，可将 pCR 率作为进一步治疗（升/降级）的早期决策点，同时结合淋巴结阴性状态和高 sTIL。有关 Sharma 的相关评论，见第 4840 页。
