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Immunotherapy for head and neck cancer: Recent advances and future directions.

ABSTRACT: Three randomized phase III trials have now conclusively proven that exposure to a PD-1 inhibitor prolongs survival in recurrent/metastatic (R/M) HNSCC, and it is clear that such agents should be used in the management of all patients who do not have contraindications to their use. Two of these phase III randomized trials showed that the anti-PD1 antibodies nivolumab and pembrolizumab were superior to investigators' choice chemotherapy in second-line platinum-refractory R/M HNSCC. Recently, a third phase III randomized trial, KEYNOTE-048, showed that pembrolizumab with chemotherapy was superior to the EXTREME regimen (cis- or carboplatin, 5-fluorouracil (5-FU) and cetuximab) in all patients, and pembrolizumab monotherapy was superior in patients whose tumors express PD-L1 in first-line R/M HNSCC. Pembrolizumab is now approved as monotherapy in PD-L1 expressing disease (combined positive score ?1) or in combination with chemotherapy for all patients with R/M HNSCC. Thus, PD-L1 biomarker testing will be routinely used in R/M HNSCC, and this employs a scoring system that incorporates immune cell staining, referred to as the combined positive score (CPS). Additionally, for the 85% of patients with PD-L1 CPS ?1, clinical judgment will guide the choice of pembrolizumab monotherapy or pembrolizumab plus chemotherapy, until more detailed clinical data are forthcoming to better inform this decision. In this article we discuss the clinical trials leading to these therapeutic advances and we will review initial results from clinical trials in previously untreated, locally advanced disease, and those using novel combinations of checkpoint inhibitors, co-stimulatory agonists, and therapeutic vaccines.

SUBMITTER: Cramer JD

PROVIDER: S-EPMC7749717 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Immunotherapy for head and neck cancer: Recent advances and future directions.

Cramer John D JD Burtness Barbara B Ferris Robert L RL

Oral oncology 20191101

Three randomized phase III trials have now conclusively proven that exposure to a PD-1 inhibitor prolongs survival in recurrent/metastatic (R/M) HNSCC, and it is clear that such agents should be used in the management of all patients who do not have contraindications to their use. Two of these phase III randomized trials showed that the anti-PD1 antibodies nivolumab and pembrolizumab were superior to investigators' choice chemotherapy in second-line platinum-refractory R/M HNSCC. Recently, a thi ...[more]

PMID: 31683169

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Project description:Prostate cancer is one of the most prevalent cancers and the second leading cause of cancer-related deaths in men in the United States. A large number of patients undergo radiation therapy (RT) as a standard care of treatment; however, RT causes erectile dysfunction (radiation-induced erectile dysfunction; RiED) because of late side effects after RT that significantly affects quality of life of prostate cancer patients. Within 5 years of RT, approximately 50% of patients could develop RiED. Based on the past and current research findings and number of publications from our group, the precise mechanism of RiED is under exploration in detail. Recent investigations have shown prostate RT induces significant morphologic arterial damage with aberrant alterations in internal pudendal arterial tone. Prostatic RT also reduces motor function in the cavernous nerve which may attribute to axonal degeneration may contributing to RiED. Furthermore, the advances in radiogenomics such as radiation induced somatic mutation identification, copy number variation and genome-wide association studies has significantly facilitated identification of biomarkers that could be used to monitoring radiation-induced late toxicity and damage to the nerves; thus, genomic- and proteomic-based biomarkers could greatly improve treatment and minimize arterial tissue and nerve damage. Further, advanced technologies such as proton beam therapy that precisely target tumor and significantly reduce off-target damage to vital organs and healthy tissues. In this review, we summarize recent advances in RiED research and novel treatment modalities for RiED. We also discuss the possible molecular mechanism involved in the development of RiED in prostate cancer patients. Further, we discuss various readily available methods as well as novel strategies such as stem cell therapies, shockwave therapy, nerve grafting with tissue engineering, and nutritional supplementations might be used to mitigate or cure sexual dysfunction following radiation treatment.

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Immunotherapy for head and neck cancer: Recent advances and future directions.

Publications

Immunotherapy for head and neck cancer: Recent advances and future directions.

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