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免疫检查点抑制剂时代的卵巢癌:现状与未来展望

Ovarian Cancer in the Era of Immune Checkpoint Inhibitors: State of the Art and Future Perspectives.

作者信息

Maiorano Brigida Anna, Maiorano Mauro Francesco Pio, Lorusso Domenica, Maiello Evaristo

机构信息

Oncology Unit, Foundation Casa Sollievo della Sofferenza IRCCS, 71013 San Giovanni Rotondo, Italy.

Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy.

出版信息

Cancers (Basel). 2021 Sep 3;13(17):4438. doi: 10.3390/cancers13174438.

Abstract

BACKGROUND

Ovarian cancer (OC) represents the eighth most common cancer and the fifth leading cause of cancer-related deaths among the female population. In an advanced setting, chemotherapy represents the first-choice treatment, despite a high recurrence rate. In the last ten years, immunotherapy based on immune checkpoint inhibitors (ICIs) has profoundly modified the therapeutic scenario of many solid tumors. We sought to summarize the main findings regarding the clinical use of ICIs in OC.

METHODS

We searched PubMed, Embase, and Cochrane Databases, and conference abstracts from international congresses (such as ASCO, ESMO, SGO) for clinical trials, focusing on ICIs both as monotherapy and as combinations in the advanced OC.

RESULTS

20 studies were identified, of which 16 were phase I or II and 4 phase III trials. These trials used ICIs targeting PD1 (nivolumab, pembrolizumab), PD-L1 (avelumab, aterolizumab, durvalumab), and CTLA4 (ipilimumab, tremelimumab). There was no reported improvement in survival, and some trials were terminated early due to toxicity or lack of response. Combining ICIs with chemotherapy, anti-VEGF therapy, or PARP inhibitors improved response rates and survival in spite of a worse safety profile.

CONCLUSIONS

The identification of biomarkers with a predictive role for ICIs' efficacy is mandatory. Moreover, genomic and immune profiling of OC might lead to better treatment options and facilitate the design of tailored trials.

摘要

背景

卵巢癌(OC)是女性中第八大常见癌症,也是癌症相关死亡的第五大主要原因。在晚期情况下,尽管复发率很高,但化疗仍是首选治疗方法。在过去十年中,基于免疫检查点抑制剂(ICI)的免疫疗法深刻改变了许多实体瘤的治疗格局。我们试图总结关于ICI在OC临床应用的主要研究结果。

方法

我们检索了PubMed、Embase和Cochrane数据库以及国际大会(如美国临床肿瘤学会、欧洲肿瘤内科学会、美国妇科肿瘤学会)的会议摘要,以查找临床试验,重点关注ICI在晚期OC中作为单药治疗和联合治疗的情况。

结果

共确定了20项研究,其中16项为I期或II期试验,4项为III期试验。这些试验使用了靶向PD1(纳武单抗、帕博利珠单抗)、PD-L1(阿维鲁单抗、阿替利珠单抗、度伐鲁单抗)和CTLA4(伊匹木单抗、曲美木单抗)的ICI。未报告生存率有改善,一些试验因毒性或无反应而提前终止。尽管安全性较差,但将ICI与化疗、抗血管内皮生长因子(VEGF)治疗或聚(ADP-核糖)聚合酶(PARP)抑制剂联合使用可提高缓解率和生存率。

结论

必须鉴定对ICI疗效具有预测作用的生物标志物。此外,OC的基因组和免疫分析可能会带来更好的治疗选择,并有助于设计针对性的试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2389/8430975/1094b58d4ad5/cancers-13-04438-g001.jpg

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