Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Oncologist. 2021 Jul;26(7):558-e1098. doi: 10.1002/onco.13682. Epub 2021 Feb 12.
Advanced germ cell tumors are aggressive and associated with poor prognosis. Pembrolizumab was overall well tolerated in 12 heavily pretreated patients. Three patients had radiographic stable disease that lasted for 10.9 months, 5.5 months, and 4.5 months, respectively. Published data of immunotherapeutic agents in patients with advanced germ cell tumors are confirmed. The limited antitumor activity of immunotherapy in germ cell tumors is, at least partially, attributed to tumor biology (low tumor mutational burden; low PD-1 expression) and other poor-risk features. Tumor profiling to understand the mechanisms of resistance to pembrolizumab and innovative clinical trials that may include immunotherapy are warranted.
Advanced germ cell tumors are associated with poor prognosis. We investigated the role of pembrolizumab in patients with advanced germ cell tumors.
We analyzed a prespecified cohort of an open-label, phase II clinical trial in which patients with advanced germ cell tumors were treated with pembrolizumab (200 mg) intravenously every 21 days. The endpoints of the study were the non-progression rate (NPR) at 27 weeks, safety, and tolerability. An NPR >20% was considered successful and worthy of further pursuit.
From August 2016 to February 2018, 12 patients (10 men, 2 women) were treated (median age, 35 years [range, 22-63 years]; median number of prior systemic therapies, 3.5 [range, 2-7]; median number of metastatic sites, 3 [range, 2-8]). Overall, pembrolizumab was well tolerated. One patient experienced both grade 1 immune-related skin rash and grade 3 immune-related pneumonitis. No patient died from toxicity. Three patients had radiographic stable disease that lasted for 10.9 months, 5.5 months, and 4.5 months, respectively. No objective response was noted. The median progression-free survival was 2.4 months (95% confidence interval [CI], 1.5-4.5 months), and the median overall survival was 10.6 months (95% CI, 4.6-27.1 months). The 27-week NPR was 9.0% (95% CI, 0.23-41.2%).
Overall, pembrolizumab was safe and had limited antitumor activity in these patients. In the advanced, metastatic setting, tumor profiling to understand the mechanisms of resistance to immunotherapy and innovative clinical trials to identify efficacious combination regimens rather than off-label use of pembrolizumab are warranted.
高级生殖细胞瘤具有侵袭性，预后不良。在 12 名预处理过的患者中，帕博利珠单抗总体耐受良好。3 名患者的影像学疾病稳定持续了 10.9 个月、5.5 个月和 4.5 个月。免疫治疗在晚期生殖细胞瘤患者中的应用的已发表数据得到了证实。免疫疗法在生殖细胞瘤中的有限抗肿瘤活性至少部分归因于肿瘤生物学（低肿瘤突变负担；低 PD-1 表达）和其他不良风险特征。有必要进行肿瘤分析以了解对帕博利珠单抗的耐药机制，并开展可能包含免疫疗法的创新临床试验。
高级生殖细胞瘤预后不良。我们研究了帕博利珠单抗在高级生殖细胞瘤患者中的作用。
我们分析了一项开放标签、二期临床试验的预设队列，该试验中，高级生殖细胞瘤患者接受帕博利珠单抗（200mg）静脉输注，每 21 天一次。该研究的终点是 27 周时的无进展率（NPR）、安全性和耐受性。NPR>20%被认为是成功的，值得进一步研究。
2016 年 8 月至 2018 年 2 月，12 名患者（10 名男性，2 名女性）接受了治疗（中位年龄 35 岁[范围 22-63 岁]；中位既往全身治疗次数 3.5[范围 2-7]；中位转移部位数 3[范围 2-8]）。总体而言，帕博利珠单抗耐受良好。1 名患者出现 1 级免疫相关皮疹和 3 级免疫相关肺炎。没有患者因毒性而死亡。3 名患者的影像学疾病稳定持续了 10.9 个月、5.5 个月和 4.5 个月。没有观察到客观缓解。中位无进展生存期为 2.4 个月（95%置信区间[CI]：1.5-4.5 个月），中位总生存期为 10.6 个月（95%CI：4.6-27.1 个月）。27 周 NPR 为 9.0%（95%CI：0.23-41.2%）。
总体而言，帕博利珠单抗在这些患者中是安全的，具有有限的抗肿瘤活性。在晚期、转移性环境中，需要进行肿瘤分析以了解对免疫治疗的耐药机制，并开展创新临床试验以确定有效的联合治疗方案，而不是进行帕博利珠单抗的非适应证使用。
