Rios-Hoyo A, Dai J, Noel T, Blenman K R M, Park T, Pusztai L
Yale Cancer Center, Yale School of Medicine, New Haven, USA; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Yale Cancer Center, Yale School of Medicine, New Haven, USA.
ESMO Open. 2025 Apr;10(4):104494. doi: 10.1016/j.esmoop.2025.104494. Epub 2025 Mar 18.
Immune-related adverse events (irAEs) have been associated with improved outcomes in different tumors; however, their impact during neoadjuvant immune checkpoint inhibitor therapy and chemotherapy in triple-negative breast cancer (TNBC) remains unknown.
This analysis included patients from a phase I/II single-arm clinical trial at Yale Cancer Center and its regional care centers. The study was conducted from December 2015 to December 2020. Eligible patients were adults aged ≥18 years with clinical stage I-III TNBC for whom systemic chemotherapy was indicated. Patients received durvalumab concomitant with nab-paclitaxel and dose-dense doxorubicin-cyclophosphamide. Durvalumab was not administered post-operatively. We examined the association of developing an irAE with pathologic complete response (pCR = ypT0/is, ypN0), residual cancer burden (RCB), event-free survival (EFS), and overall survival (OS). A landmark analysis from the time of surgery was also carried out.
A total of 67 patients were eligible for toxicity and efficacy analysis; of these, 27 had irAEs of any grade and 13 had multiple irAEs. The median follow-up was 61 months (range 6.8-94.03 months). The most frequent irAEs were dermatologic (n = 14), endocrine (n = 13), and gastrointestinal (n = 5). Patients who experienced irAEs achieved a pCR or RCB 0-1 rate of 56% and 73%, respectively, compared with 40% and 55% in those without irAEs (P = 0.309 and 0.19). Development of irAE was also associated with significantly improved EFS [hazard ratio (HR) 0.25; 95% confidence interval (CI) 0.09-0.66, P = 0.024] and a trend for improved OS (HR 0.42; 95% CI 0.14-1.27, P = 0.17). Patients with more than one irAE had no EFS events. The landmark analysis showed similar results (EFS HR 0.19, P = 0.014; OS HR 0.4, P = 0.16).
The development of irAE was associated with numerically improved pCR rates, lower RCB, and significantly higher EFS in patients treated with neoadjuvant immune checkpoint therapy plus chemotherapy.
免疫相关不良事件（irAE）与不同肿瘤的预后改善相关；然而，它们在三阴性乳腺癌（TNBC）新辅助免疫检查点抑制剂治疗和化疗期间的影响尚不清楚。
本分析纳入了来自耶鲁癌症中心及其区域护理中心的一项I/II期单臂临床试验的患者。该研究于2015年12月至2020年12月进行。符合条件的患者为年龄≥18岁、临床分期为I-III期TNBC且需要进行全身化疗的成年人。患者接受度伐利尤单抗联合白蛋白结合型紫杉醇和剂量密集型阿霉素-环磷酰胺治疗。度伐利尤单抗术后未给药。我们研究了发生irAE与病理完全缓解（pCR = ypT0/is，ypN0）、残余癌负担（RCB）、无事件生存期（EFS）和总生存期（OS）之间的关联。还进行了从手术时间开始的标志性分析。
共有67例患者符合毒性和疗效分析条件；其中，27例发生了任何级别的irAE，13例发生了多种irAE。中位随访时间为61个月（范围6.8 - 94.03个月）。最常见的irAE为皮肤毒性（n = 14）、内分泌毒性（n = 13）和胃肠道毒性（n = 5）。发生irAE的患者pCR或RCB 0 - 1率分别为56%和73%，而未发生irAE的患者分别为40%和55%（P = 0.309和0.19）。irAE的发生还与EFS显著改善相关[风险比（HR）0.25；95%置信区间（CI）0.09 - 0.66，P = 0.024]以及OS改善趋势相关（HR 0.42；95% CI 0.14 - 1.27，P = 0.17）。发生多种irAE的患者无EFS事件。标志性分析显示了相似的结果（EFS HR 0.19，P = 0.014；OS HR 0.4，P = 0.16）。
在接受新辅助免疫检查点治疗加化疗的患者中，irAE的发生与pCR率数值上的改善、较低的RCB以及显著更高的EFS相关。
