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Pembrolizumab and head and neck

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https://www.readbyqxmd.com/read/29726785/medication-use-evaluation-of-programmed-death-1-inhibitors-in-a-veteran-population
#1
Vivianne Nguyen, Mostaqul Huq
Objectives To evaluate the safety and efficacy of programmed death-1 immune checkpoint inhibitors in a clinical practice setting. Methods Chart reviews were conducted on a total of 21 Veterans with advanced or metastatic cancers treated with programmed death-1 checkpoint inhibitors between 1 January 2015 and 31 July 2017. Among them, 16 patients were treated with nivolumab, including 12 with non-small cell lung cancer, 2 with melanoma, and 2 with bladder cancer. Pembrolizumab was used in 5 patients, including 4 with melanoma and 1 with head and neck cancer...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29709262/new-therapies-in-head-and-neck-cancer
#2
REVIEW
Rodell T Santuray, Daniel E Johnson, Jennifer R Grandis
Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with high rates of mortality and morbidity. Beginning with cetuximab, investigators continue to optimize antibody technology to target cell-surface receptors that promote HNSCC growth. Small molecules and oligonucleotides have also emerged as therapeutic inhibitors of key receptor-mediated signaling pathways. Although many such therapies have been disappointing in clinical trials as single agents, they continue to be studied in combination with standard therapies...
May 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29666026/cervical-cancer-state-of-the-science-from-angiogenesis-blockade-to-checkpoint-inhibition
#3
REVIEW
Lindsey E Minion, Krishnansu S Tewari
Vascular endothelial growth factor (VEGF) has emerged as a therapeutic target in several malignancies, including cervical cancer. Chemotherapy doublets combined with the fully humanized monoclonal antibody, bevacizumab, now constitute first-line therapy for women struggling with recurrent/metastatic cervical carcinoma. Regulatory approval for this indication was based on the phase III randomized trial, GOG 240, which demonstrated a statistically significant and clinically meaningful improvement in overall survival when bevacizumab was added to chemotherapy: 17...
March 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29548299/severe-immune-mucositis-and-esophagitis-in-metastatic-squamous-carcinoma-of-the-larynx-associated-with-pembrolizumab
#4
Fanny Zulay Acero Brand, Nicolas Suter, Jean-Philippe Adam, Bernard Faulques, Antonio Maietta, Denis Soulières, Normand Blais
BACKGROUND: Pembrolizumab is an anti-programmed death 1 (PD-1) receptor monoclonal antibody that has shown activity as second line treatment for metastatic head and neck squamous cell carcinoma (HNSCC). Immune-related adverse events are now well described complications of PD-1 inhibitors and most organ sites have been shown to be potentially affected. CASE PRESENTATION: We describe a 69-year old patient with a relapsed squamous cell carcinoma of the supraglottic larynx with lung metastasis after receiving adjuvant concurrent cisplatin and radiotherapy...
March 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29497306/new-developments-in-the-management-of-head-and-neck-cancer-impact-of-pembrolizumab
#5
REVIEW
Khalil Saleh, Roland Eid, Fady Gh Haddad, Nadine Khalife-Saleh, Hampig Raphaël Kourie
Head and neck squamous cell carcinoma (HNSCC), a heterogeneous group of upper aerodigestive tract malignancies, is the seventh most common cancer worldwide. Tobacco use and alcohol consumption were the most identified risk factors of HNSCC. However, human papilloma virus, a sexually transmitted infection, has been determined as another primary cause of HNSCC. Early-stage disease is treated with surgery or radiotherapy. Recurrent or metastatic HNSCC is associated with poor prognosis with a median overall survival of 10 months...
2018: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29464975/pembrolizumab-and-its-use-in-the-treatment-of-recurrent-or-metastatic-head-and-neck-cancer
#6
Siddharth Sheth, Jared Weiss
Until recently, palliative options for the treatment of platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have been cytotoxic chemotherapy and EGFR inhibitors. These agents offer limited efficacy with substantial toxicity. The development of novel immune checkpoint inhibitors has challenged the standard treatment. Pembrolizumab is a potent and highly selective humanized monoclonal antibody that blocks the interaction between PD-1, an immune checkpoint receptor and its ligands PD-L1 and -2...
February 21, 2018: Future Oncology
https://www.readbyqxmd.com/read/29441454/chemotherapy-and-immunotherapy-for-recurrent-and-metastatic-head-and-neck-cancer-a-systematic-review
#7
REVIEW
Alessandro Guidi, Carla Codecà, Daris Ferrari
Head and neck cancer (HNC) is a fatal malignancy with an overall long-term survival of about 50% for all stages. The diagnosis is not rarely delayed, and the majority of patients present with loco-regionally advanced disease. The rate of second primary tumors after a diagnosis of HNC is about 3-7% per year, the highest rate among solid tumors. Currently, a single-modality or a combination of surgery, radiotherapy and chemotherapy (CHT), is the standard treatment for stage III-IV HNC. For the recurrent/metastatic setting, in the last 40 years great efforts have been made in order to develop a more effective CHT regimen, from the use of methotrexate alone, to the combination of cisplatin (CDDP) and 5-fluorouracile (5FU) or paclitaxel...
February 13, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29432222/immunotherapy-for-recurrent-metastatic-head-and-neck-cancer
#8
Salvatore Alfieri, Stefano Cavalieri, Lisa Licitra
PURPOSE OF REVIEW: In the last decade, after cetuximab (anti-epidermal growth factor receptor), none of the novel investigated compounds has demonstrated benefit in head and neck squamous cell cancers (HNSCC), both in advanced and curative settings. Therefore, prognosis of recurrent/metastatic (R/M) HNSCC patients remains dismal, especially in platinum-refractory cohort. In the last few years, a new important class of drugs has affirmed its role. HNSCC, even if less 'immunogenic' than other malignancies (e...
April 2018: Current Opinion in Otolaryngology & Head and Neck Surgery
https://www.readbyqxmd.com/read/29416641/-pd-l1-cd274-and-pd-l2-pdcd1lg2-promoter-methylation-is-associated-with-hpv-infection-and-transcriptional-repression-in-head-and-neck-squamous-cell-carcinomas
#9
Alina Franzen, Timo J Vogt, Tim Müller, Jörn Dietrich, Andreas Schröck, Carsten Golletz, Peter Brossart, Friedrich Bootz, Jennifer Landsberg, Glen Kristiansen, Dimo Dietrich
Background: DNA methylation of the immune checkpoint gene PD-L1 has recently been shown to be associated with PD-L1 mRNA expression in various malignancies. This study aimed to investigate the association of PD-L1 and PD-L2 methylation with mRNA expression, immune cell infitration, protein expression and human papilloma virus (HPV) infection in head and neck squamous cell carcinoma (HNSCC) patients. Results: DNA methylation of PD-L1 and PD-L2 correlates inversely with mRNA expression ( PD-L1 : p ≤ 0...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29384959/pembrolizumab-for-recurrent-metastatic-head-and-neck-squamous-cell-carcinoma-in-an-asian-population
#10
Wen-Chun Chen, Pen-Yuan Chu, Yu-Ting Lee, Wen-Bin Lu, Chun-Yu Liu, Peter Mu-Hsin Chang, Muh-Hwa Yang
Head and neck squamous cell carcinoma (HNSCC) has a high prevalence and is a major cause of cancer deaths in Taiwan. However, there is still no effective salvage therapy that prolongs the life expectancy of patients with recurrent/metastatic (R/M) HNSCC. Immune checkpoint therapy that targets the programmed cell death protein 1 (PD-1) may provide clinical benefit for these patients. We analyzed 22 R/M HNSCC patients who received pembrolizumab, a monoclonal antibody against PD-1, as salvage therapy. Intravenous pembrolizumab was given at a fixed dosage of 100 or 200 mg every 3 weeks...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29355614/head-and-neck-squamous-cell-carcinoma-genomics-and-emerging-biomarkers-for-immunomodulatory-cancer-treatments
#11
REVIEW
Benjamin Solomon, Richard J Young, Danny Rischin
Head and neck squamous cell carcinoma (HNSCC) comprises a heterogeneous group of tumors that arise from the squamous epithelium of the oral cavity, oropharynx, larynx and hypopharynx. While many HNSCCs are related to classical etiologic factors of smoking and alcohol, a clinically, genomically, and immunologically distinct subgroup of tumors arise from the epithelium of the tonsil and the base of tongue as a result of infection with Human Papilloma Virus (HPV). In this review we describe the genomic and immunologic landscape of HNSCC, highlighting differences between HPV-positive and HPV-negative HNSCC...
January 30, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29348866/protein-methyltransferases-and-demethylases-dictate-cd8-t-cell-exclusion-in-squamous-cell-carcinoma-of-the-head-and-neck
#12
Theodore Vougiouklakis, Riyue Bao, Yusuke Nakamura, Vassiliki Saloura
A subset of patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) benefit from pembrolizumab and nivolumab, but the majority of patients do not probably due to lack of activated cytotoxic CD8+ T-cells in their tumor tissues. Herein, we aim to investigate whether specific protein methyltransferases (PMTs) and demethylases (PDMTs) could play any roles in the CD8+ T-cell exclusion process in HPV-negative SCCHN. RNA sequencing data from the TCGA database were interrogated for HPV-negative SCCHN patients using a 10-gene chemokine signature that classifies SCCHN tissues into CD8+ T-cell inflamed and non-CD8+ T-cell inflamed phenotypes...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340043/clinical-significance-of-yap1-activation-in-head-and-neck-squamous-cell-carcinoma
#13
Young-Gyu Eun, Dongjin Lee, Young Chan Lee, Bo Hwa Sohn, Eui Hyun Kim, Sun Young Yim, Kee Hwan Kwon, Ju-Seog Lee
By analyzing the genomic data of head and neck squamous cell cancer (HNSCC), we investigated clinical significance of YAP1 activation. Copy number and mRNA expression of YAP1 were analyzed together to assess clinical relevance of YAP1 activation in HNSCC. The clinical significance of YAP1 activation was further validated in four independent test cohorts. We also assessed the correlation of YAP1 activation with genomic alterations such as copy number alteration, somatic mutation, and miRNA expression. The YAP1-activated (YA) subgroup showed worse prognosis for HNSCC as tested and validated in five cohorts...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29284202/pembrolizumab-in-asia-pacific-patients-with-advanced-head-and-neck-squamous-cell-carcinoma-analyses-from-keynote-012
#14
MULTICENTER STUDY
Makoto Tahara, Kei Muro, Yasuhisa Hasegawa, Hyun Cheol Chung, Chia-Chi Lin, Bhumsuk Keam, Kenichi Takahashi, Jonathan D Cheng, Yung-Jue Bang
KEYNOTE-012 was a phase Ib, multicohort study designed to investigate efficacy and safety of pembrolizumab in advanced solid tumors. Results from the subset of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) from the Asia-Pacific region are reported. Patients with recurrent/metastatic HNSCC, measurable disease (RECIST version 1.1), and ECOG performance status (PS) 0-1 were eligible for enrollment in the HNSCC expansion cohort. Patients received pembrolizumab 200 mg every 3 weeks...
March 2018: Cancer Science
https://www.readbyqxmd.com/read/29231907/activated-hgf-c-met-axis-in-head-and-neck-cancer
#15
REVIEW
Levi Arnold, Jonathan Enders, Sufi Mary Thomas
Head and neck squamous cell carcinoma (HNSCC) is a highly morbid disease. Recent developments including Food and Drug Administration (FDA) approved molecular targeted agent's pembrolizumab and cetuximab show promise but did not improve the five-year survival which is currently less than 40%. The hepatocyte growth factor receptor; also known as mesenchymal-epithelial transition factor (c-Met) and its ligand hepatocyte growth factor (HGF) are overexpressed in head and neck squamous cell carcinoma (HNSCC); and regulates tumor progression and response to therapy...
December 12, 2017: Cancers
https://www.readbyqxmd.com/read/29185392/immunotherapy-in-head-and-neck-cancer-evidence-and-perspectives
#16
Alicia Tosoni, Enrico Franceschi, Ernesto Pasquini, Andrea Lanese, Elisa Donini, Maria Pia Foschini, Danilo Dall'Olio, Alba A Brandes
Head and neck squamous cell carcinomas evade immune response through multiple immunologic resistance mechanisms. Two of the most commonly involved checkpoint inhibitory mechanisms are CTLA-4 and PD-1/PD-L1, which act at earlier and later stages of immune response to tumors. Pembrolizumab and nivolumab are PD-1 antibodies that interrupt the immunosuppressive pathway of inhibitory checkpoints, which are used by tumor cells to prevent immune reaction. Both recently gained US FDA approval for the treatment of patients with recurrent or metastatic head and neck cancer with disease progression during or following platinum containing chemotherapy...
December 2017: Immunotherapy
https://www.readbyqxmd.com/read/29156447/pd-1-blockade-in-advanced-nsclc-a-focus-on-pembrolizumab
#17
REVIEW
Solange Peters, Keith M Kerr, Rolf Stahel
Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers and is responsible for a large proportion of all cancer-related deaths. Current treatment options are inadequate, reflecting a substantial unmet clinical need. Increasing knowledge regarding the mechanisms and genetic aberrations underlying tumor development and growth has heralded a new era of therapy in oncology, moving away from indiscriminate cytotoxic chemotherapy toward more finely focused, targeted medicine. The development of small-molecule drugs and monoclonal antibodies directed toward specific components of dysfunctional molecular or immune pathways, and mutated genes specific to particular cancer types, is leading the field to more personalized and less toxic treatment options, many of which have demonstrated greater efficacy and survival benefits than their chemotherapeutic counterparts...
January 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29069302/mechanistic-overview-of-immune-checkpoints-to-support-the-rational-design-of-their-combinations-in-cancer-immunotherapy
#18
A Rotte, J Y Jin, V Lemaire
Checkpoint receptor blockers, known to act by blocking the pathways that inhibit immune cell activation and stimulate immune responses against tumor cells, have been immensely successful in the treatment of cancer. Among several checkpoint receptors of immune cells, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), T-cell immunoglobulin and ITIM domain (TIGIT), T-cell immunoglobulin-3 (TIM-3) and lymphocyte activation gene 3 (LAG-3) are the most commonly targeted checkpoints for cancer immunotherapy...
January 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28923211/nivolumab-and-pembrolizumab-monoclonal-antibodies-against-programmed-cell-death-1-pd-1-that-are-interchangeable
#19
REVIEW
Vinay Prasad, Victoria Kaestner
Nivolumab (Opdivo, Bristol Meyer Squibb, New York, NY) and pembrolizumab (Keytruda, Merck, Kenilworth, NJ) are the first two US Food and Drug Administration (FDA)-approved monoclonal antibodies targeting programmed death-1 (PD-1). Nivolumab and pembrolizumab work by interfering with the interaction between PD-1 and programmed death ligand-1 (PD-L1), whose unimpeded interaction downregulates T cells allowing cancer cells to evade immune surveillance. These drugs have earned a series of FDA approvals for melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), urothelial cancer, classical Hodgkin lymphoma, and renal cell cancer...
April 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28919706/profile-of-pembrolizumab-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma-design-development-and-place-in-therapy
#20
REVIEW
Sulsal Haque, Mahender Yellu, Jaskirat Randhawa, Nooshin Hashemi-Sadraei
Head and neck squamous cell cancer (HNSCC) is the sixth most common malignancy worldwide, and despite advances in cytotoxic, surgical and radiation techniques, outcomes are still poor in those with both locally advanced and metastatic diseases. The need for development of better therapeutics along with a greater understanding of the relationship between the immune system and malignancies has led to a new therapeutic modality, immune modulators, particularly checkpoint inhibitors in HNSCC. It is now well recognized that HNSCC circumvents crucial pathways utilized by the immune system to escape surveillance...
2017: Drug Design, Development and Therapy
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