背景:基于Keynote-522(KN-522)临床试验中更高的无事件生存率和病理完全缓解(pCR),Pembrolizumab联合新辅助化疗(NAC)是早期三阴性乳腺癌(TNBC)的当前护理标准。然而,这种积极的五药方案与免疫相关不良事件(irAEs)的风险增加相关.我们调查了该方案的真实世界临床结果和毒性以及pCR和irAE的预测因素。
方法:我们确定并提取了2021年7月1日至2023年12月31日在美国4个学术机构接受KN-522方案治疗的153例早期TNBC患者的数据。进行了单因素和多因素分析,以确定与pCR和irAE相关的因素.
结果:中位年龄为52岁(四分位距,42-60年),66%的白人和24%的黑人患者的I/II期(67%),淋巴结阴性疾病(58%),3级(86%)肿瘤,和≥1合并症(68%)。大约21%的人停用了帕博利珠单抗,因为毒性;50%接受较低的相对剂量强度(RDI)的化疗(剂量减少或停药)。153名患者中,99例(64.7%)实现了pCR,83例(54%)经历了irAE,18人(12%)的IRAE≥3级。在新辅助期期间观察到大多数(90%)的irAE。I/II期与III期疾病(OR1.55,CI1.04-2.33,P=0.03),在多变量分析中,年龄(OR0.96,CI0.93-0.99,P=.01)和完全与降低的NACRDI(OR1.53,CI1.04-2.26,P=.03)与较高的pCR率相关.pembrolizumab的周期越少,irAE的可能性越高(OR1.52,CI1.07-2.16,P=.02),可能是由于在发生iriAE的患者中早期停药和接受少于8个周期的派博利珠单抗。
结论:我们的研究验证了KN-522方案的临床疗效;然而,我们观察到在这个现实世界的人群中,irAE的发生率较高(54%)。较低的阶段和较年轻的年龄与实现pCR的较高可能性相关。观察到毒性相关的化疗剂量减少或停止对实现pCR的可能性产生不利影响。
BACKGROUND: Pembrolizumab combined with neoadjuvant chemotherapy (NAC) is the current standard of care in early stage triple-negative breast cancer (TNBC) based on higher event-free survival and pathological complete response (pCR) in Keynote-522 (KN-522) clinical trial. However, this aggressive five-drug regimen is associated with increased risks for immune-related adverse events (irAEs). We investigated real-world clinical outcomes and toxicity of this regimen as well as factors predictive of pCR and irAEs.
METHODS: We identified and abstracted data from 153 early-stage TNBC patients treated with the KN-522 regimen between July 1, 2021, and December 31, 2023, at 4 academic institutions in the U.S. Descriptive analysis was conducted, univariate and multivariate analyses were performed to identify factors associated with pCR and irAEs.
RESULTS: The median age was 52 years (interquartile range, 42-60years), with 66% White and 24% Black patients with stage I/II (67%), node-negative disease (58%), grade 3 (86%) tumors, and ≥1 comorbidities (68%). Approximately 21% discontinued pembrolizumab, because of toxicity; ∼50% received a lower relative dose intensity (RDI) of chemotherapy (dose reduction or discontinuation). Of the 153 patients, 99 (64.7%) achieved pCR and 83 (54%) experienced an irAE, with 18 (12%) having ≥ grade 3 irAE. The majority (90%) of the irAEs were observed during neoadjuvant phase. Stage I/II versus stage III disease (OR 1.55, CI 1.04-2.33, P = .03), age (OR 0.96, CI 0.93-0.99, P = .01) and full versus reduced RDI of NAC (OR 1.53, CI 1.04-2.26, P = .03) were associated with higher pCR rates on multivariate analyses. Fewer cycles of pembrolizumab were associated with a higher likelihood of irAEs (OR 1.52, CI 1.07-2.16, P = .02), likely explained by the early discontinuation and receipt of less than 8 cycles of pembrolizumab in patients who experienced irAEs.
CONCLUSIONS: Our study validates the clinical efficacy of KN-522 regimen; however, we observed a higher incidence of irAEs (54%) in this real-world population. Lower stage and younger age were associated with higher likelihood of achieving pCR. Toxicity-related chemotherapy dose reduction or discontinuation was observed to adversely impact the likelihood of achieving pCR.