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PD-1 抑制疗法治疗晚期皮肤鳞状细胞癌:来自南加州大学的回顾性分析。

PD-1 inhibition therapy for advanced cutaneous squamous cell carcinoma: a retrospective analysis from the University of Southern California.

机构信息

USC Norris Comprehensive Cancer Center, 1441 Eastlake Ave, NTT 3449, Los Angeles, CA, 90033, USA.

Department of Dermatology, USC Keck School of Medicine, Los Angeles, CA, USA.

出版信息

J Cancer Res Clin Oncol. 2021 Jun;147(6):1803-1811. doi: 10.1007/s00432-020-03458-6. Epub 2020 Nov 18.

Abstract

PURPOSE

Approximately 5% of patients with cutaneous squamous cell carcinoma (CSCC) may develop recurrent or metastatic disease. The management of such cases is challenging and requires multi-disciplinary care. Immunotherapy using PD-1 inhibition was approved to treat unresectable or metastatic CSCC in 2018. Given limited data regarding clinical outcomes outside of published trials, we describe our experience using this therapy.

METHODS

We retrospectively reviewed all patients treated with PD-1 inhibition as therapy for locally advanced, regionally metastatic or distant metastatic CSCC at the University of Southern California. Clinicopathological characteristics, treatment data using PD-1 inhibitors, and outcomes were assessed.

RESULTS

Among 26 patients treated with PD-1 inhibition, the objective response rate was 42.3%, with 19.2% of patients having partial response and 23.1% having complete response to therapy. The median progression-free survival was 5.4 months. Median tumor mutational burden (TMB) was higher among responders compared to non-responders (60 vs. 9 Mut/Mb, p = 0.04). Primary CSCC tumor location on the head/neck was also associated with response to PD-1 inhibition (p = 0.04). Two patients with mutations affecting mismatch repair deficiency were noted to have complete response to treatment. No other variables were associated with treatment outcomes.

CONCLUSION

PD-1 inhibition produces durable responses among patients with advanced or metastatic CSCC. PD-1 inhibition therapy is well tolerated, but patients should be monitored closely for immune-related adverse events, particularly frail or immune-suppressed patients. Further investigation of potential biomarkers to help identify patients who will derive the most benefit from this therapeutic option is needed.

摘要

目的

大约有 5%的皮肤鳞状细胞癌(CSCC)患者可能会出现复发或转移性疾病。对于这些病例的治疗具有挑战性,需要多学科的护理。PD-1 抑制的免疫疗法于 2018 年被批准用于治疗不可切除或转移性 CSCC。鉴于在已发表的试验之外,关于临床结果的数据有限,我们描述了使用该疗法的经验。

方法

我们回顾性地审查了南加州大学治疗局部晚期、区域性转移或远处转移性 CSCC 的所有接受 PD-1 抑制治疗的患者。评估了临床病理特征、使用 PD-1 抑制剂的治疗数据和结果。

结果

在接受 PD-1 抑制治疗的 26 名患者中,客观缓解率为 42.3%,其中 19.2%的患者有部分缓解,23.1%的患者有完全缓解。无进展生存期的中位数为 5.4 个月。与无反应者相比,反应者的肿瘤突变负荷(TMB)更高(60 对 9 Mut/Mb,p=0.04)。原发 CSCC 肿瘤位于头颈部与对 PD-1 抑制的反应相关(p=0.04)。有 2 例存在影响错配修复缺陷的突变的患者对治疗有完全反应。没有其他变量与治疗结果相关。

结论

PD-1 抑制在晚期或转移性 CSCC 患者中产生持久的反应。PD-1 抑制治疗耐受性良好,但应密切监测免疫相关不良事件,尤其是体弱或免疫抑制的患者。需要进一步研究潜在的生物标志物,以帮助确定从这种治疗选择中获益最多的患者。

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