An increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal^1,2,3. We conducted a single-arm, phase 2 study of pembrolizumab in patients with solid tumor malignancies and LMD (NCT02886585). Patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity. The primary endpoint was rate of overall survival at 3 months (OS3). Secondary objectives included toxicity, response rate and time to intracranial or extracranial disease progression. A Simon two-stage design was used to compare a null hypothesis OS3 of 18% against an alternative of 43%. Twenty patients—17 with breast cancer, two with lung cancer and one with ovarian cancer—were enrolled into the pre-specified evaluation group having received at least one dose of pembrolizumab. The median follow-up of surviving patients was 6.3 months (range, 2.2–12.5 months). The percentage of patients who experienced one (or more) grade 3 or higher adverse events at least possibly related to treatment was 40%, the most frequent being hyperglycemia (n = 6), nausea (n = 7) and vomiting (n = 7). The study met the primary endpoint, as 12 of 20 (OS3, 0.60; 90% confidence interval, 0.39–0.78) patients were alive at 3 months after enrollment. Pembrolizumab is safe and feasible and displays promising activity in patients with LMD. Further investigations are needed to identify which patients with LMD can benefit from pembrolizumab.

越来越多的转移性癌症患者会发展出脑膜脑膜疾病（LMD），生存率低下^1,2,3。我们在实体瘤恶性肿瘤和LMD（NCT02886585）患者中进行了单抗派姆单抗的2期研究。患者每3周静脉注射200 mg派姆单抗，直至确定​​的进展或出现无法接受的毒性。主要终点是3个月时的总生存率（OS3）。次要目标包括毒性，对颅内或颅外疾病进展的反应率和时间。使用西蒙的两阶段设计来比较18％的原假设OS3和43％的原假设OS3。预先确定的评估组招募了20名患者（其中17名患有乳腺癌，2名患有肺癌和1名患有卵巢癌），他们接受了至少一剂pembrolizumab。存活患者的中位随访时间为6.3个月（范围2.2–12.5个月）。n  = 6），恶心（n  = 7）和呕吐（n  = 7）。该研究达到了主要终点，入选后3个月有20名患者中有12名（OS3，0.60； 90％置信区间，0.39-0.78）存活。派姆单抗是安全可行的，在LMD患者中显示出有希望的活性。需要进一步的研究以确定哪些LMD患者可以从pembrolizumab中受益。