Redondo Andres, Gallego Alejandro, Mendiola Marta
Department of Medical Oncology, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
Translational Oncology Research Laboratory, Instituto de Investigación Hospital La Paz (IdiPAZ), Madrid, Spain.
Expert Rev Clin Pharmacol. 2022 Jan;15(1):1-9. doi: 10.1080/17512433.2022.2044791. Epub 2022 Feb 22.
Between 20% and 30% of the endometrial cancers (EC) are associated with a deficiency of a mismatch repair (MMRd) protein or high microsatellite instability (MSI-H), characteristics that render the tumor more sensitive to immune checkpoint inhibitors. There is no standard treatment for advanced EC after progression to a platinum-containing regimen.
The phase I GARNET clinical trial assessed the safety, tolerability, and antitumor activity of anti-PD1 dostarlimab in patients with advanced solid tumors. The A1 cohort of this trial enrolled patients with MMRd or MSI-H recurrent or advanced EC who had previously received a platinum-containing regimen. The results of this cohort showed significant clinical activity, durable responses, and a favorable safety profile, without reducing quality of life. Based on these data, dostarlimab achieved accelerated approval.
Although a randomized study has not yet been conducted, dostarlimab monotherapy should be the treatment of choice for patients with advanced MMRd EC in progression after a platinum-containing regimen. Selecting patients with EC for immune checkpoint inhibitors using the MMRd predictive biomarker could facilitate more efficient and sustainable health systems and avoid the use of more toxic combinations, leading to personalized medicine.
20%至30%的子宫内膜癌（EC）与错配修复（MMRd）蛋白缺陷或高微卫星不稳定性（MSI-H）相关，这些特征使肿瘤对免疫检查点抑制剂更敏感。进展至含铂方案后，晚期EC尚无标准治疗方法。
I期GARNET临床试验评估了抗PD1多斯塔利单抗在晚期实体瘤患者中的安全性、耐受性和抗肿瘤活性。该试验的A1队列纳入了既往接受过含铂方案的MMRd或MSI-H复发性或晚期EC患者。该队列的结果显示出显著的临床活性、持久反应和良好的安全性，且未降低生活质量。基于这些数据，多斯塔利单抗获得了加速批准。
尽管尚未进行随机研究，但多斯塔利单抗单药治疗应是含铂方案进展后的晚期MMRd EC患者的首选治疗方法。使用MMRd预测生物标志物为EC患者选择免疫检查点抑制剂可促进更高效和可持续的卫生系统，并避免使用毒性更大的联合方案，从而实现个性化医疗。
