Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
Expert Rev Anticancer Ther. 2022 Oct;22(10):1029-1038. doi: 10.1080/14737140.2022.2125382. Epub 2022 Sep 19.
Outcomes for patients with advanced cutaneous squamous cell carcinoma (cSCC) are poor, however recent approvals in programmed death-1 (PD-1) checkpoint inhibition have shown promise. Prior systemic treatments in this patient population included chemotherapy and anti-EGFR directed therapies, with limited long-term benefit. Studies investigating cemiplimab and pembrolizumab have recently revealed significant responses with many cases of sustained benefit in both locally advanced and recurrent and/or metastatic disease. While these treatments have shown improvement in outcomes, there are continued areas of need.
This review focuses on clinical evidence for PD-1 directed checkpoint inhibition in advanced cSCC. Excluded populations and new approaches involving immunotherapy are discussed.
Immune checkpoint inhibition in advanced cSCC has shown impressive benefit. The clinical trials for both cemiplimab and pembrolizumab demonstrate similar responses and outcomes. Biomarkers for predicting response are an area of need. In addition, these trials excluded immunosuppressed patients due to hematological malignancies or prior organ transplant, which are populations with significantly increased risk of cSCC. Finally, a variety of novel approaches using checkpoint inhibition in cSCC are being investigated, with some encouraging preliminary results.
晚期皮肤鳞状细胞癌(cSCC)患者的预后较差,但最近程序性死亡-1(PD-1)检查点抑制剂的批准显示出了希望。该患者人群中先前的系统治疗包括化疗和抗 EGFR 靶向治疗,但长期获益有限。最近的研究表明,cemilimab 和 pembrolizumab 具有显著的疗效,许多局部晚期、复发性和/或转移性疾病患者都能从中获得持续的益处。虽然这些治疗方法改善了患者的预后,但仍有一些需要解决的问题。
本综述重点关注 PD-1 定向检查点抑制在晚期 cSCC 中的临床证据。讨论了排除人群和涉及免疫疗法的新方法。
晚期 cSCC 的免疫检查点抑制显示出令人印象深刻的益处。cemilimab 和 pembrolizumab 的临床试验均显示出相似的疗效和结果。预测反应的生物标志物是一个需要解决的问题。此外,这些试验由于血液系统恶性肿瘤或先前的器官移植而排除了免疫抑制患者,因为这些患者患 cSCC 的风险显著增加。最后,正在研究使用 cSCC 中的检查点抑制的各种新方法,一些初步结果令人鼓舞。