Bogani Giorgio, Moore Kathleen N, Ray-Coquard Isabelle, Lorusso Domenica, Matulonis Ursula A, Ledermann Jonathan A, González-Martín Antonio, Kurtz Jean-Emmanuel, Pujade-Lauraine Eric, Scambia Giovanni, Caruso Giuseppe, Raspagliesi Francesco, Colombo Nicoletta, Monk Bradley J
Deaprtment of Gynecologic Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
Stephenson Cancer Center at the University of Oklahoma Health Sciences Center/Sarah Cannon Research Institute, Oklahoma City, OK, United States.
Gynecol Oncol. 2025 Feb;193:30-40. doi: 10.1016/j.ygyno.2024.12.011. Epub 2025 Jan 6.
Therapeutic interventions for epithelial ovarian cancer (EOC) have increased greatly over the last decade but improvements outside of biomarker selected therapies have been limited. There remains a pressing need for more effective treatment options that can prolong survival and enhance the quality of life of patients with EOC. In contrast to the significant benefits of immunotherapy with immune checkpoint inhibitors (CPI) seen in many solid tumors, initial experience in EOC suggests limited efficacy of CPIs monotherapy.
A systematic review of phase III studies testing the role of CPIs in ovarian cancer was performed.
Seven randomized trials testing CPIs in newly diagnosed (n = 3) and recurrent (n = 4) EOC are evaluated. Overall, those trials included data of 5671 patients. Single-agent PD-L1 inhibitor trials have not shown significant efficacy in newly diagnosed ovarian cancer. Triplet maintenance with bevacizumab plus olaparib and durvalumab is associated with longer progression-free survival than maintenance with bevacizumab alone in patients without tumor BRCA mutations. CPIs were not effective in platinum-sensitive (n = 1031) and platinum-resistant (n = 1420) EOC.
The value of adding CPI to standard treatment including poly (ADP-ribose) polymerase (PARP) inhibitors with or without bevacizumab remains unclear and is being addressed in ongoing clinical trials. The combination of cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) inhibitors may enhance the efficacy of immunotherapy in EOC and studies are underway to investigate the combination of CPI with other emerging treatment modalities. PROSPERO registration ID: CRD42024536017.
在过去十年中，上皮性卵巢癌（EOC）的治疗干预措施有了很大增加，但除生物标志物选择的治疗方法外，其他方面的改善有限。仍然迫切需要更有效的治疗选择，以延长EOC患者的生存期并提高其生活质量。与免疫检查点抑制剂（CPI）免疫疗法在许多实体瘤中显示出的显著益处形成对比的是，EOC的初步经验表明CPI单药治疗的疗效有限。
对测试CPI在卵巢癌中作用的III期研究进行了系统评价。
评估了七项在新诊断（n = 3）和复发性（n = 4）EOC中测试CPI的随机试验。总体而言，这些试验纳入了5671例患者的数据。单药PD-L1抑制剂试验在新诊断的卵巢癌中未显示出显著疗效。在没有肿瘤BRCA突变的患者中，贝伐单抗加奥拉帕利和度伐鲁单抗三联维持治疗比单独使用贝伐单抗维持治疗的无进展生存期更长。CPI在铂敏感（n = 1031）和铂耐药（n = 1420）的EOC中均无效。
在包括聚（ADP-核糖）聚合酶（PARP）抑制剂（有或没有贝伐单抗）的标准治疗中添加CPI的价值仍不明确，正在进行的临床试验正在探讨这一问题。细胞毒性T淋巴细胞相关蛋白4（CTLA-4）和程序性细胞死亡蛋白1（PD-1）抑制剂的联合使用可能会提高EOC免疫治疗的疗效，目前正在进行研究以探讨CPI与其他新兴治疗方式的联合应用。PROSPERO注册编号：CRD42024536017。
