本研究旨在评估pembrolizumab介导的程序性细胞死亡蛋白1抑制加放疗(RT)在未选择程序性死亡配体1表达的转移性三阴性乳腺癌患者中的疗效和安全性。
目前的研究是单臂,西蒙2级,2期临床试验共纳入17名患者,中位年龄为52岁(范围,37-73岁)。以5个每日分数递送3000厘米灰色(cGy)的RT剂量。Pembrolizumab在第一个RT部分的3天内以200mg的剂量静脉内施用,然后每3周±3天直到疾病进展。中位随访时间为34.5周(范围,2.1-108.3周)。本研究的主要终点是使用实体瘤的反应评估标准(RECIST;1.1版)测量的未照射病变患者在第13周的总反应率(ORR)。次要终点包括安全性和无进展生存期。探索性目标是确定预测ORR和无进展生存期的生物标志物。
整个队列的ORR为17.6%(17例患者中有3例;95%CI,4.7%-44.2%),有3个完整的响应(CR),1例病情稳定,进展性疾病13例。由于疾病进展,八名患者在第13周之前死亡。在第13周使用RECIST1.1版进行评估的9名女性中,第3周(33%)获得了CR,在被照射的门静脉外,肿瘤体积减少了100%。CR持续18周,20周,108周,分别。最常见的1至2级毒性(根据美国国家癌症研究所常见不良事件术语标准进行评估,4.0版)为皮炎(29%)。四个3级不良事件归因于pembrolizumab:疲劳,淋巴细胞减少,和感染。无4级不良事件或治疗相关死亡报告。
发现pembrolizumab和RT的组合是安全的,并且在预后不良的患者中表现出令人鼓舞的活性。转移性,未选择程序性死亡-配体1表达的三阴性乳腺癌。需要更大规模的检查点阻断加RT与反应的预测生物标志物的临床试验。
The current
study was conducted to evaluate the efficacy and safety of pembrolizumab-mediated programmed cell death protein 1 inhibition plus radiotherapy (RT) in patients with metastatic triple-negative breast cancer who were unselected for programmed death-ligand 1 expression.
The current
study was a single-arm, Simon 2-stage, phase 2 clinical
trial that enrolled a total of 17 patients with a median age of 52 years (range, 37-73 years). An RT dose of 3000 centigrays (cGy) was delivered in 5 daily fractions. Pembrolizumab was administered intravenously at a dose of 200 mg within 3 days of the first RT fraction, and then every 3 weeks ± 3 days until disease progression. The median follow-up was 34.5 weeks (range, 2.1-108.3 weeks). The primary endpoint of the current
study was the overall response rate (ORR) at week 13 in patients with unirradiated lesions measured using Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Secondary endpoints included safety and progression-free survival. Exploratory objectives were to identify biomarkers predictive of ORR and progression-free survival.
The ORR for the entire cohort was 17.6% (3 of 17 patients; 95% CI, 4.7%-44.2%), with 3 complete responses (CRs), 1 case of stable disease, and 13 cases of progressive disease. Eight patients died prior to week 13 due to disease progression. Among the 9 women assessed using RECIST version 1.1 at week 13, 3 (33%) achieved a CR, with a 100% reduction in tumor volume outside of the irradiated portal. The CRs were durable for 18 weeks, 20 weeks, and 108 weeks, respectively. The most common grade 1 to 2 toxicity (assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) was dermatitis (29%). Four grade 3 adverse events were attributed to pembrolizumab: fatigue, lymphopenia, and infection. No were no grade 4 adverse events or treatment-related deaths reported.
The combination of pembrolizumab and RT was found to be safe and demonstrated encouraging activity in patients with poor-prognosis, metastatic, triple-negative breast cancer who were unselected for programmed death-ligand 1 expression. Larger clinical trials of checkpoint blockade plus RT with predictive biomarkers of response are needed.