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Update on immune checkpoint inhibitors in gynecological cancers.

ABSTRACT: In recent years, progress in our understanding of immune-modulatory signaling pathways in immune cells and the tumor microenvironment (TME) has led to rejuvenated interest in cancer immunotherapy. In particular, immunotherapy targeting the immune checkpoint receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell-death 1 (PD-1), and programmed cell-death ligand 1 (PD-L1) have demonstrated clinical activity in a wide variety of tumors, including gynecological cancers. This review will focus on the emerging clinical data on the therapeutic role of immune checkpoint inhibitors, and potential strategies to enhance the efficacy of this class of compounds, in the context of gynecological cancers. It is anticipated that future biomarker-directed clinical trials will provide further insights into the mechanisms underlying response and resistance to immunotherapy, and help guide our approach to designing therapeutic combinations that have the potential to enhance the benefit of immunotherapy in patients with gynecologic cancers.

SUBMITTER: Heong V

PROVIDER: S-EPMC5323287 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Update on immune checkpoint inhibitors in gynecological cancers.

Heong Valerie V Ngoi Natalie N Tan David Shao Peng DS

Journal of gynecologic oncology 20161214 2

In recent years, progress in our understanding of immune-modulatory signaling pathways in immune cells and the tumor microenvironment (TME) has led to rejuvenated interest in cancer immunotherapy. In particular, immunotherapy targeting the immune checkpoint receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell-death 1 (PD-1), and programmed cell-death ligand 1 (PD-L1) have demonstrated clinical activity in a wide variety of tumors, including gynecological cancer ...[more]

PMID: 28028993

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Project description:Advanced and recurrent gynecological cancers are associated with a poor prognosis and there is still a lack of effective treatments. Immune checkpoint blockade (ICB) therapy is an important element of cancer-targeted therapy and immunotherapy. The programed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) pathways are the two main targets of ICB. In this study, we provide a comprehensive review of clinical evidence concerning ICB therapy in gynecological cancers and discuss future implications. All clinical trials of ICB therapy in gynecological cancers were reviewed. We searched ClinicalTrials.gov to collect data from completed and ongoing clinical trials. The clinical evidence regarding the efficacy of ICB agents in gynecological cancers were discussed. Six phase III clinical trials have reported their results of primary outcomes, and a total of 25 phase II clinical trials have been completed. As revealed in phase III trials, pembrolizumab (a PD-1 antibody) improved the overall survival and progression-free survival in endometrial cancer patients with mismatch repair deficiency and cervical cancer patients with expressions of PD-L1. Based on these findings, pembrolizumab was approved by the Food and Drug Administration and European Medicines Agency as a cancer medication used to treat certain patients with endometrial cancer or cervical cancer. Other PD-1 antibodies, including dostarlimab and cemiplimab, also showed antitumor efficacy in clinical trials. Dostarlimab treatment showed an encouraging response rate in endometrial cancer patients with mismatch repair deficiency. Cemiplimab treatment led to a longer overall survival and a lower risk of death than chemotherapy among patients with recurrent cervical cancer. Three completed phase III trials investigated anti-PD-L1 agents (atezolizumab and avelumab) in the treatment of ovarian cancer. The results were not encouraging. Other strategies of ICB therapy which had showed potential clinical benefit in the treatment of gynecological cancers in early-phase trials need to be further evaluated in late-stage trials. The antitumor efficacy of ICB therapy is promising, and the key to making further progress in the treatment of gynecological cancers is to identify more biomarkers and explore innovative combination treatments with other targeted therapies.

Dataset Information

Update on immune checkpoint inhibitors in gynecological cancers.

Publications

Update on immune checkpoint inhibitors in gynecological cancers.

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