Pembrolizumab for the treatment of cervical cancer

Marret, Grégoire; Borcoman, Édith; Tourneau, Christophe Le

doi:10.1080/14712598.2019.1646721

Cited by 36 publications

(34 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…20 The advent of PD1/PD-L1 inhibitors breaks through the therapeutic bottle neck and may change the traditional treatment model. 9,21 The combination of chemotherapy and immunotherapy has been shown to improve treatment effects. Some studies suggested a synergistic interrelation of chemo and immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

<p>The Combined Use of Chemotherapy and Radiotherapy with PD-1 Inhibitor, Pembrolizumab, in Advanced Cervical Cancer: A Case Report</p>

Lyu

Shen

Beharee

et al. 2020

OTT

View full text Add to dashboard Cite

As a result of the limited therapeutic options, advanced cervical cancer is difficult to treat, making the prognosis poor. Therefore, new therapeutic modalities or combinations need to be explored. We herein reported a case of stage IVB cervical cancer which was irresponsive to chemotherapy alone. Based on previous studies and after patient's consent was obtained, we made a therapeutic plan: chemotherapy (albumin-bound paclitaxel and carboplatin) combined with immunotherapy (PD-1 inhibitor pembrolizumab). After 6 cycles of combined treatment, the patient got almost complete resolution with slight advent event. The treatment was further supported by local radiotherapy combined with immunotherapy. During the treatment period, disease was relatively stable, but the patient suffered severe grade 4 myelosuppression. We were therefore left with no other choice than to interrupt both chemotheraphy and radiotherapy. Before long, the tumor grew explosively again. These guided us to conclude that the combination use of albumin-bound paclitaxel (nabpaclitaxel) and carboplatin and pembrolizumab is effective and well tolerated in the treatment of advanced cervical cancer. The combined use of radiotherapy and pembrolizumab may also be effective. However, the combination use of chemotherapy, radiotherapy and immunotherapy in advanced cancer has not been well studied, and there are still many unsolved queries.

show abstract

Section: Discussionmentioning

confidence: 99%

<p>The Combined Use of Chemotherapy and Radiotherapy with PD-1 Inhibitor, Pembrolizumab, in Advanced Cervical Cancer: A Case Report</p>

Lyu

Shen

Beharee

et al. 2020

OTT

View full text Add to dashboard Cite

show abstract

“…Of note, the FDA also concurrently approved the PD-L1 immunohistochemistry 22C3 pharmDx test (Dako Agilent) as a companion diagnostic test to guide the patient selection process for pembrolizumab treatment (63). This is critically important since pembrolizumab as a single agent exhibits a limited efficacy in recurrent and/or metastatic setting in an unselected patient population (61). Moreover, an ongoing phase III trial (KEYNOTE-826 phase III trial, NCT03635567) aims to treat advanced or recurrent cervical cancer in the first line using pembrolizumab or a placebo plus one of four platinum-and taxane-based chemotherapy regimens (61).…”

Section: Pd-1 Checkpoints and Cervical Cancermentioning

confidence: 99%

“…This is critically important since pembrolizumab as a single agent exhibits a limited efficacy in recurrent and/or metastatic setting in an unselected patient population (61). Moreover, an ongoing phase III trial (KEYNOTE-826 phase III trial, NCT03635567) aims to treat advanced or recurrent cervical cancer in the first line using pembrolizumab or a placebo plus one of four platinum-and taxane-based chemotherapy regimens (61). Notably, patients are being stratified based on PD-L1 expression (combined positive score ≥1) by immunohistochemistry (62,63).…”

Section: Pd-1 Checkpoints and Cervical Cancermentioning

confidence: 99%

“…In this context, pembrolizumab, an immune checkpoint inhibitor, represents a full-length human IgG4/kappa monoclonal antibody that is directed against the PD-1 protein ( 60 , 61 ) and has been approved by the FDA as a second-line treatment for recurrent or metastatic carcinomas of the cervix, non-small cell lung, and urothelial as well as malignant melanoma ( 60 ). Pembrolizumab (Keytruda) was approved for the treatment of patients with recurrent and/or metastatic cervical cancer in 2018 based on the KEYNOTE 158 (NCT02628067) Phase II study which involved 98 patients with recurrent and/or metastatic cervical carcinomas ( 62 ).…”

Section: Pd-1 Checkpoints and Cervical Cancermentioning

confidence: 99%

“…HPV is a non-enveloped doublestranded DNA virus that encompasses more than 150 types. On the basis of oncogenicity, HPVs are classified into high-risk (16,18,31,33,35,39,45,51,52,56,58,59,68,69,82) and low-risk (6,8,11,40,42,43,44,54,61,72) (5), of which high-risk HPV types 16 and 18 are the most widespread carcinogenic strains to humans. Additionally, results from case-control studies report a convincing association between high-risk HPV types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66 and carcinogenesis (5).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

High-Risk HPV Oncoproteins and PD-1/PD-L1 Interplay in Human Cervical Cancer: Recent Evidence and Future Directions

et al. 2020

View full text Add to dashboard Cite

Cervical cancer is the fourth most common malignancy in women worldwide and a leading cause of cancer-related mortality in developing countries. Important etiological factors in this cancer are high-risk human papillomaviruses (HPV), as roughly 96% of cervical cancer cases are positive for these oncoviruses. On the other hand, it has been recently pointed out that E6/E7 oncoproteins of high-risk HPV can upregulate the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) axis. Likewise, several recent reports showed that checkpoint blockades targeting PD-1/PD-L1 pathways have achieved efficient clinical responses via suppressing cancer progression and improving survival in several types of human cancers including metastatic cervical cancer. In this review, we summarize recent advances in our understanding of the PD-1/PD-L1 signaling pathway and its interaction with high-risk HPV and their oncoproteins, which could have an important impact on the management of HPV-associated cancers including cervical.

show abstract

NAT10/ac4C/FOXP1 Promotes Malignant Progression and Facilitates Immunosuppression by Reprogramming Glycolytic Metabolism in Cervical Cancer

Chen,

Hao,

Liu

et al. 2023

Advanced Science

View full text Add to dashboard Cite

Immunotherapy has recently emerged as the predominant therapeutic approach for cervical cancer (CCa), driven by the groundbreaking clinical achievements of immune checkpoint inhibitors (ICIs), such as anti‐PD‐1/PD‐L1 antibodies. N4‐acetylcytidine (ac4C) modification, catalyzed by NAT10, is an important posttranscriptional modification of mRNA in cancers. However, its impact on immunological dysregulation and the tumor immunotherapy response in CCa remains enigmatic. Here, a significant increase in NAT10 expression in CCa tissues is initially observed that is clinically associated with poor prognosis. Subsequently, it is found that HOXC8 activated NAT10 by binding to its promoter, thereby stimulating ac4C modification of FOXP1 mRNA and enhancing its translation efficiency, eventually leading to induction of GLUT4 and KHK expression. Moreover, NAT10/ac4C/FOXP1 axis activity resulted in increased glycolysis and a continuous increase in lactic acid secretion by CCa cells. The lactic acid‐enriched tumor microenvironment (TME) further contributed to amplifying the immunosuppressive properties of tumor‐infiltrating regulatory T cells (Tregs). Impressively, NAT10 knockdown enhanced the efficacy of PD‐L1 blockade‐mediated tumor regression in vivo. Taken together, the findings revealed the oncogenic role of NAT10 in initiating crosstalk between cancer cell glycolysis and immunosuppression, which can be a target for synergistic PD‐1/PD‐L1 blockade immunotherapy in CCa.

show abstract

Pembrolizumab for the treatment of cervical cancer

Cited by 36 publications

References 74 publications

<p>The Combined Use of Chemotherapy and Radiotherapy with PD-1 Inhibitor, Pembrolizumab, in Advanced Cervical Cancer: A Case Report</p>

<p>The Combined Use of Chemotherapy and Radiotherapy with PD-1 Inhibitor, Pembrolizumab, in Advanced Cervical Cancer: A Case Report</p>

High-Risk HPV Oncoproteins and PD-1/PD-L1 Interplay in Human Cervical Cancer: Recent Evidence and Future Directions

NAT10/ac4C/FOXP1 Promotes Malignant Progression and Facilitates Immunosuppression by Reprogramming Glycolytic Metabolism in Cervical Cancer

Contact Info

Product

Resources

About