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Current Treatment Landscape of Nasopharyngeal Carcinoma and Potential Trials Evaluating the Value of Immunotherapy.

ABSTRACT: Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer with a distinctive regional and racial prevalence. It is associated with Epstein-Barr virus infection and has a high propensity for regional and distant metastases, while it is very sensitive to radiation and chemotherapy. A common feature of Epstein-Barr virus-positive NPC is the dense infiltration of lymphocytes in the tumor stroma and positive programmed death-ligand 1 expression in tumor cells, making it an attractive target for immunotherapy, especially immune checkpoint inhibitors. As new immunotherapeutic agents are being rapidly adopted in many cancers, including head and neck cancer, the National Cancer Institute sponsored a clinical trial planning meeting to identify opportunities for developing phase II and III trials testing immunotherapy in different stages of NPC. The meeting started with the summary of the biology of the disease, current standards of care, and evidence of immunotherapy in this cancer. Three subcommittees were tasked to develop clinical trials: loco regionally advanced, nonmetastatic NPC; widely metastatic NPC; and either local recurrence after initial treatment or presenting with oligometastatic disease. This article summarizes the proceedings of this clinical trial planning meeting and provides a road map for future trials incorporating immune checkpoint inhibitors for therapeutic management of NPC. This road map, though specific for NPC, may also be applicable to other virally driven cancers that have similar ability to evade the host's immune system.

SUBMITTER: Le QT

PROVIDER: S-EPMC7962891 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Current Treatment Landscape of Nasopharyngeal Carcinoma and Potential Trials Evaluating the Value of Immunotherapy.

Le Quynh Thu QT Colevas A Dimitrios AD O'Sullivan Brian B Lee Anne W M AWM Lee Nancy N Ma Brigette B Siu Lillian L LL Waldron John J Lim Chwee-Ming CM Riaz Nadeem N Lynn Jean J Malik Shakun S

Journal of the National Cancer Institute 20190701 7

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer with a distinctive regional and racial prevalence. It is associated with Epstein-Barr virus infection and has a high propensity for regional and distant metastases, while it is very sensitive to radiation and chemotherapy. A common feature of Epstein-Barr virus-positive NPC is the dense infiltration of lymphocytes in the tumor stroma and positive programmed death-ligand 1 expression in tumor cells, making it an attractive target fo ...[more]

PMID: 30912808

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Project description:Nasopharyngeal carcinoma (NPC) has seen improved treatment outcomes and a decrease in incidence worldwide in recent years due to developments in medicine and improved public health. However, 70% of cases are still diagnosed at advanced stages and these advanced NPC cases show a poor prognosis. Reports on current and future treatment in advanced NPC are summarized. Chemoradiotherapy is the mainstay of treatment for advanced NPC. The administration of platinum agents as a concurrent drug and intensity modulated radiotherapy (IMRT) is the most appropriate irradiation method, and is associated with high local control rates. For induction and adjuvant chemotherapy, platinum-based two- or three-drug combination chemotherapy is recommended. The tumour volume, plasma Epstein-Barr virus (EBV)-DNA levels, and the tumour site are used to determine the indication for adjuvant and neo-adjuvant chemotherapy. The tolerability of induction chemotherapy is controversial, and the indications and timing should be carefully considered in each case. Chemotherapy is used for patients with distant metastasis. Gemcitabine/cisplatin is the first-line regimen. The efficacy of immune checkpoint inhibitor (ICI) treatment has recently been reported for NPC and, as in other areas of the head and neck, it is expected to be effective for patients with recurrent/distant metastasis. Trials are underway for various uses of ICIs, including induction chemotherapy, postoperative treatment, and use in combination with chemoradiotherapy. Immunotherapy for NPC, an EBV-associated cancer, has been reported to have some efficacy with immunotherapy used in other EBV-associated cancers. Immunotherapy may be introduced for NPC in the future, depending on the results of clinical trials. Future changes in the treatment of NPC are expected to include risk classification based on plasma EBV-DNA levels and the development of personalized treatment with individual selection of timing and type of therapy.

Project description:In this article, we focus on the current and emerging treatments in nasopharyngeal cancer (NPC). A detailed evolution of the current standard of care, and new techniques and treatment options will be reviewed. Intergroup 0099 established the role for chemoradiotherapy (chemo-RT) in the treatment of nasopharyngeal carcinoma. Multiple randomized Phase III trials have shown the benefit of chemo-RT; however, none of these studies utilized modern radiotherapy (RT) techniques of intensity-modulated radiation therapy (IMRT). IMRT has the ability to deliver high doses of radiation to the target structures while sparing adjacent bystander healthy tissues, and has now become the preferred RT treatment modality. Chemotherapy also has had a shifting paradigm of induction and/or adjuvant chemotherapy combined with RT alone, to the investigation with concurrent chemo-RT. New treatment options including targeted monoclonal antibodies and small molecule tyrosine kinase inhibitors are being studied in NPC. These new biologic therapies have promising in vitro activity for NPC, and emerging clinical studies are beginning to define their role. RT continues to expand its capabilities, and since IMRT and particle therapy, specifically intensity-modulated proton therapy (IMPT), has reports of impressive dosimetric efficacy in-silica. Adaptive RT is attempting to reduce toxicity while maintaining treatment efficacy, and the clinical results are still in their youth. Lastly, Epstein- Barr virus (EBV) DNA has recently been studied for prediction of tumor response and its use as a biomarker is increasingly promising to aid in early detection as well as supplementing the current staging system. RT with or without chemotherapy remains the standard of care for nasopharyngeal carcinoma. Advances in RT technique, timing of chemotherapy, biologically targeted agents, particle therapy, adaptive RT, and the incorporation of EBV DNA as a biomarker may aid in the current and future treatment of nasopharyngeal cancer.

Dataset Information

Current Treatment Landscape of Nasopharyngeal Carcinoma and Potential Trials Evaluating the Value of Immunotherapy.

Publications

Current Treatment Landscape of Nasopharyngeal Carcinoma and Potential Trials Evaluating the Value of Immunotherapy.

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