Department of Hematology and Oncology, Wilmot Cancer Institute, Rochester, NY, USA.
Department of Internal Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Oncologist. 2022 Jul 5;27(7):525-531. doi: 10.1093/oncolo/oyac095.
As the use of immune checkpoint inhibitors (ICIs) in treating a variety of cancer types has increased in recent years, so too have the number of reports on patients acquiring resistance to these therapies. Overcoming acquired resistance to immunotherapy remains an important need in the field of immuno-oncology. Herein, we present a case that suggests sequential administration of combination immunotherapy may be beneficial to advanced cervical cancer patients exhibiting acquired resistance to mono-immunotherapy. The patient's tumor is microsatellite instability-high (MSI-H), which is an important biomarker in predicting ICI response. Results from recent interim prospective studies using combination immunotherapy (eg, nivolumab and ipilimumab) with anti-PD-1 plus anti-CTLA-4 inhibitor following progression on anti-PD-1 inhibitors (eg, nivolumab) have shown anti-tumor activity in patients with advanced melanoma and metastatic urothelial carcinoma. We also introduce retrospective studies and case reports/case series of dual checkpoint inhibition with anti-PD-1 inhibitor plus anti-CTLA-4 inhibitor after progression on prior anti-PD/PD-L1 monotherapy. To date, there has been no prospective study on the use of combined anti-PD-1 and anti-CTLA-4 therapy at the time of progression on anti-PD-1 therapy in patients with MSI-H tumors or advanced cervical cancer. In this report, we provide evidence that supports future investigations into such treatments.
近年来，随着免疫检查点抑制剂（ICIs）在治疗多种癌症类型中的应用增加，报道患者对这些治疗产生耐药性的数量也在增加。克服免疫治疗的获得性耐药仍然是免疫肿瘤学领域的一个重要需求。在此，我们报告了一例病例，提示序贯联合免疫治疗可能对表现出单免疫治疗获得性耐药的晚期宫颈癌患者有益。该患者的肿瘤为微卫星不稳定高（MSI-H），这是预测ICI 反应的重要生物标志物。最近使用联合免疫治疗（如纳武单抗和伊匹单抗）治疗进展后抗 PD-1 抑制剂（如纳武单抗）的前瞻性研究结果表明，联合免疫治疗在晚期黑色素瘤和转移性尿路上皮癌患者中具有抗肿瘤活性。我们还介绍了回顾性研究和双重检查点抑制的病例报告/病例系列，即在先前抗 PD/PD-L1 单药治疗进展后使用抗 PD-1 抑制剂加抗 CTLA-4 抑制剂。迄今为止，在 MSI-H 肿瘤或晚期宫颈癌患者进展时使用联合抗 PD-1 和抗 CTLA-4 治疗的前瞻性研究尚未进行。在本报告中，我们提供了支持未来此类治疗研究的证据。
