Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA.
J Natl Cancer Inst. 2023 Dec 6;115(12):1605-1615. doi: 10.1093/jnci/djad155.
Treatment options for penile squamous cell carcinoma are limited. We sought to investigate clinical outcomes and safety profiles of patients with penile squamous cell carcinoma receiving immune checkpoint inhibitors.
This retrospective study included patients with locally advanced or metastatic penile squamous cell carcinoma receiving immune checkpoint inhibitors between 2015 and 2022 across 24 centers in the United States, Europe, and Asia. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Objective response rates were determined per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events, version 5.0. Two-sided statistical tests were used for comparisons.
Among 92 patients, 8 (8.7%) were Asian, 6 (6.5%) were Black, and 24 (29%) were Hispanic and/or Latinx. Median (interquartile range) age was 62 (53-70) years. In all, 83 (90%) had metastatic penile squamous cell carcinoma, and 74 (80%) had received at least second-line treatment. Most patients received pembrolizumab monotherapy (n = 26 [28%]), combination nivolumab-ipilimumab with or without multitargeted tyrosine kinase inhibitors (n = 23 [25%]), or nivolumab (n = 16 [17%]) or cemiplimab (n = 15 [16%]) monotherapies. Median overall and progression-free survival were 9.8 months (95% confidence interval = 7.7 to 12.8 months) and 3.2 months (95% confidence interval = 2.5 to 4.2 months), respectively. The objective response rate was 13% (n = 11/85) in the overall cohort and 35% (n = 7/20) in patients with lymph node-only metastases. Visceral metastases, Eastern Cooperative Oncology Group (ECOG) performance status of 1 or higher, and a higher neutrophil/lymphocyte ratio were associated with worse overall survival. Treatment-related adverse events occurred in 27 (29%) patients, and 9.8% (n = 9) of the events were grade 3 or higher.
Immune checkpoint inhibitors are active in a subset of patients with penile squamous cell carcinoma. Future translational studies are warranted to identify patients more likely to derive clinical benefit from immune checkpoint inhibitors.
阴茎鳞状细胞癌的治疗选择有限。我们旨在研究接受免疫检查点抑制剂治疗的阴茎鳞状细胞癌患者的临床结局和安全性特征。
这项回顾性研究纳入了 2015 年至 2022 年间在美国、欧洲和亚洲的 24 个中心接受免疫检查点抑制剂治疗的局部晚期或转移性阴茎鳞状细胞癌患者。使用 Kaplan-Meier 法估计总生存期和无进展生存期。根据实体瘤反应评价标准 1.1 确定客观缓解率。根据不良事件通用术语标准 5.0 分级治疗相关不良事件。使用双侧统计检验进行比较。
在 92 名患者中，8 名（8.7%）为亚洲人，6 名（6.5%）为黑人，24 名（29%）为西班牙裔和/或拉丁裔。中位（四分位间距）年龄为 62（53-70）岁。所有患者均为转移性阴茎鳞状细胞癌（83[90%]），74 例（80%）接受了至少二线治疗。大多数患者接受了 pembrolizumab 单药治疗（n=26[28%]）、nivolumab-ipilimumab 联合或不联合多靶点酪氨酸激酶抑制剂治疗（n=23[25%]）、nivolumab 单药治疗（n=16[17%]）或 cemiplimab 单药治疗（n=15[16%]）。中位总生存期和无进展生存期分别为 9.8 个月（95%置信区间：7.7-12.8 个月）和 3.2 个月（95%置信区间：2.5-4.2 个月）。在整个队列中，客观缓解率为 13%（n=11/85），在仅有淋巴结转移的患者中为 35%（n=7/20）。内脏转移、东部肿瘤协作组（ECOG）体力状态 1 或更高、中性粒细胞/淋巴细胞比值较高与总生存期较差相关。27 名（29%）患者发生治疗相关不良事件，9.8%（n=9）为 3 级或更高。
免疫检查点抑制剂在阴茎鳞状细胞癌患者的亚组中具有活性。未来的转化研究有必要确定更有可能从免疫检查点抑制剂中获益的患者。
