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Pembrolizumab and head and neck

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https://www.readbyqxmd.com/read/28619999/pd-l2-expression-in-human-tumors-relevance-to-anti-pd-1-therapy-in-cancer
#1
Jennifer H Yearley, Christopher Gibson, Ni Yu, Christina Moon, Erin Murphy, Jonathan Juco, Jared Lunceford, Jonathan Cheng, Laura Q M Chow, Tanguy Y Seiwert, Masahisa Handa, Joanne E Tomassini, Terrill McClanahan
Purpose: Tumor-associated PD-L1 expression is predictive of clinical response to PD-1-directed immunotherapy. However, PD-L1-negative patients may also respond to PD-1 checkpoint blockade, suggesting that other PD-1 ligands may be relevant to the clinical activity of these therapies. The prevalence of PD-L2, the other known ligand of PD-1, and its relationship to response to anti-PD-1 therapy were evaluated.Experimental Design: PD-L2 expression was assessed in archival tumor tissue from seven indications using a novel immunohistochemical assay...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28602169/toxicities-of-systemic-agents-in-squamous-cell-carcinoma-of-the-head-and-neck-scchn-a-new-perspective-in-the-era-of-immunotherapy
#2
REVIEW
Nabil F Saba, Mayur D Mody, Elaine S Tan, Harpaul S Gill, Alessandra Rinaldo, Robert P Takes, Primož Strojan, Dana M Hartl, Jan B Vermorken, Missak Haigentz, Alfio Ferlito
Squamous cell carcinoma of the head and neck (SCCHN) is a difficult to treat malignancy and represents the seventh most common cancer worldwide. Systemic therapy has a critical role in the treatment of locally advanced and recurrent/metastatic disease. Cytotoxic chemotherapy has been primarily used along with radiation and surgery, with cisplatin being the standard of care choice of therapy. When contraindications to cisplatin exist, other agents such as carboplatin, taxanes, 5-fluorouracil, and cetuximab are used...
July 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28581126/systemic-therapy-for-head-and-neck-squamous-cell-carcinoma-historical-perspectives-and-recent-breakthroughs
#3
REVIEW
Michael A Blasco, Peter F Svider, S Naweed Raza, John R Jacobs, Adam J Folbe, Pankhoori Saraf, Jean Anderson Eloy, Soly Baredes, Andrew M Fribley
OBJECTIVES: Despite dramatic developments in drugs established for other malignancies, historically there have been few novel systemic agents available for the management of head and neck squamous cell carcinoma (HNSCC). However, the last decade has observed increased interest in targeted therapies for HNSCC. In 2006, cetuximab became the first major drug for HNSCC to gain Food and Drug Administration (FDA) approval in 3 decades. Recently, both pembrolizumab and nivolumab gained FDA approval for treatment of recurrent or metastatic HNSCC, and trials for other indications in HNSCC are actively underway...
June 5, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28573468/time-dependent-pharmacokinetics-of-pembrolizumab-in-patients-with-solid-tumor-and-its-correlation-with-best-overall-response
#4
Hongshan Li, Jingyu Yu, Chao Liu, Jiang Liu, Sriram Subramaniam, Hong Zhao, Gideon M Blumenthal, David C Turner, Claire Li, Malidi Ahamadi, Rik de Greef, Manash Chatterjee, Anna G Kondic, Julie A Stone, Brian P Booth, Patricia Keegan, Atiqur Rahman, Yaning Wang
Pembrolizumab is a monoclonal antibody that targets the programmed death-1 receptor to induce immune-mediated clearance (CL) of tumor cells. Originally approved by the US Food and Drug Administration in 2014 for treating patients with unresectable or metastatic melanoma, pembrolizumab is now also used to treat patients with non-small-cell lung cancer, classical Hodgkin lymphoma, head and neck cancer, and urothelial cancer. This paper describes the recently identified feature of pembrolizumab pharmacokinetics, the time-dependent or time-varying CL...
June 1, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28571578/immunotherapy-in-head-and-neck-cancer-aiming-at-extreme-precision
#5
Petr Szturz, Jan B Vermorken
BACKGROUND: Locoregionally advanced, recurrent, and metastatic squamous cell carcinomas of the head and neck (SCCHN) remain difficult to treat disease entities, in which systemic treatment often forms an integral part of their management. Immunotherapy is based on functional restoration of the host immune system, helping to counteract various tumour evasion strategies. Broadly, immunotherapeutic approaches encompass tumour-specific antibodies, cancer vaccines, cytokines, adoptive T-cell transfer, and immune-modulating agents...
June 2, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28557105/major-response-to-pembrolizumab-in-two-patients-with-locally-advanced-cutaneous-squamous-cell-carcinoma
#6
E Degache, J Crochet, N Simon, M Tardieu, S Trabelsi, M Moncourier, I Templier, L Foroni, A Lemoigne, N Pinel, H Gil, L Bouillet, M T Leccia, J Charles
Cutaneous squamous cell carcinomas (CSCC) are one of the most frequent types of cancer, with rising incidence rates(1). While the majority are cured with surgery, some CSCC are associated with significant morbidity and mortality due to their local extension and metastatic potential. The recommended treatment for these advanced stages includes radiotherapy, conventional chemotherapy, or cetuximab, which tends to yield modest responses and a high prevalence of toxic effects(2). Anti- Programmed Death-1 (PD-1) therapies recently showed their efficacy in several types of tumour, especially in patients with recurrent or metastatic head and neck squamous cell carcinomas that has continued to progress despite standard-of-care treatment, suggesting the potentical efficacy of anti-PD1 in CSCC (3,4)...
May 30, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28536670/evidence-based-treatment-options-in-recurrent-and-or-metastatic-squamous-cell-carcinoma-of-the-head-and-neck
#7
REVIEW
Athanassios Argiris, Kevin J Harrington, Makoto Tahara, Jeltje Schulten, Pauline Chomette, Ana Ferreira Castro, Lisa Licitra
The major development of the past decade in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) was the introduction of cetuximab in combination with platinum plus 5-fluorouracil chemotherapy (CT), followed by maintenance cetuximab (the "EXTREME" regimen). This regimen is supported by a phase 3 randomized trial and subsequent observational studies, and it confers well-documented survival benefits, with median survival ranging between approximately 10 and 14 months, overall response rates between 36 and 44%, and disease control rates of over 80%...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28533473/u-s-food-and-drug-administration-approval-summary-pembrolizumab-for-the-treatment-of-recurrent-or-metastatic-head-and-neck-squamous-cell-carcinoma-with-disease-progression-on-or-after-platinum-containing-chemotherapy
#8
Erin Larkins, Gideon M Blumenthal, Weishi Yuan, Kun He, Rajeshwari Sridhara, Sriram Subramaniam, Hong Zhao, Chao Liu, Jingyu Yu, Kirsten B Goldberg, Amy E McKee, Patricia Keegan, Richard Pazdur
On August 5, 2016, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA injection, Merck Sharp & Dohme Corp., Kenilworth, NJ) for treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. Approval was based on the objective response rate (ORR) and duration of response (DoR) in a cohort of patients in a nonrandomized multi-cohort trial (KEYNOTE-012) that included 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy...
May 22, 2017: Oncologist
https://www.readbyqxmd.com/read/28515943/evaluation-of-dosing-strategy-for-pembrolizumab-for-oncology-indications
#9
Tomoko Freshwater, Anna Kondic, Malidi Ahamadi, Claire H Li, Rik de Greef, Dinesh de Alwis, Julie A Stone
BACKGROUND: Traditionally, most monoclonal antibodies (mAbs) have been dosed based on body weight because of perceived contribution of body size in pharmacokinetic variability. The same approach was used in the initial pembrolizumab studies; however, following availability of PK data, the need for weight-based dosing for pembrolizumab was reassessed. METHODS: A previously established population PK (popPK) model as well as exposure-response results from patients with advanced melanoma or non-small cell lung cancer (NSCLC) were used to evaluate the potential application of a fixed dosing regimen with the aim of maintaining pembrolizumab exposures within the range demonstrated to provide near maximal efficacy and acceptable safety...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28487385/immune-related-gene-expression-profiling-after-pd-1-blockade-in-non-small-cell-lung-carcinoma-head-and-neck-squamous-cell-carcinoma-and-melanoma
#10
Aleix Prat, Alejandro Navarro, Laia Paré, Noemí Reguart, Patricia Galvan, Tomás Pascual, Alex Martínez, Paolo Nuciforo, Laura Comerma, Llucia Alos, Nuria Pardo, Susana Cedrés, Cheng Fan, Joel S Parker, Lydia Gaba, Ivan Victoria, Nuria Viñolas, Ana Vivancos, Ana Arance, Enriqueta Felip
Antibody targeting of the immune checkpoint receptor PD1 produces therapeutic activity in a variety of solid tumors, but most patients exhibit partial or complete resistance to treatment for reasons that are unclear. In this study, we evaluated tumor speciments from 65 patients with melanoma, lung non-squamous, squamous cell lung or head and neck cancers who were treated with the approved PD1 targeting antibodies pembrolizumab or nivolumab. Tumor RNA before anti-PD1 therapy was analyzed on the nCounter system using the PanCancer 730-Immune Panel, and we identified 23 immune-related genes or signatures linked to response and progression-free survival (PFS)...
May 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28485332/current-status-of-systemic-therapy-for-recurrent-and-or-metastatic-squamous-cell-carcinoma-of-the-head-and-neck
#11
REVIEW
L A Jacob, T Chaudhuri, K C Lakshmaiah, K G Babu, L Dasappa, McS Babu, A H Rudresha, K N Lokesh, L K Rajeev
Head and neck squamous cell carcinoma (HNSCC) is now the seventh most common cancer worldwide. The median overall survival for patients with recurrent and/or metastatic (R/M) HNSCC remains <1 year despite modern systemic chemotherapy and targeted agents. Palliative systemic therapy for patients with R/M HNSCC typically includes a platinum-based doublet, with an understanding that the increase in efficacy compared with single agents is primarily related to improved response rate, and not survival. Till date, the only systemic therapy regimen to demonstrate survival superiority over platinum-5-fluorouracil (5-FU) doublet is platinum, FU, and cetuximab...
October 2016: Indian Journal of Cancer
https://www.readbyqxmd.com/read/28467522/eruptive-keratoacanthomas-associated-with-pembrolizumab-therapy
#12
Azael Freites-Martinez, Bernice Y Kwong, Kerri E Rieger, Daniel G Coit, A Dimitrios Colevas, Mario E Lacouture
Importance: To our knowledge, there have been no previous reports of eruptive keratoacanthomas (KAs) in patients receiving pembrolizumab. Objective: To report the cases of 3 consecutive patients with pembrolizumab-induced eruptive KAs and their management. Design, Setting, and Participants: Case report study of 3 patients from 2 centers with pembrolizumab-treated cancer who all developed eruptive KAs. Interventions: All 3 patients had AK treatment with clobetasol ointment and intralesional triamcinolone; 2 patients also underwent open superficial cryosurgery...
May 3, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28464441/current-studies-of-immunotherapy-in-head-and-neck-cancer
#13
Volkan Dogan, Thorsten Rieckmann, Adrian Münscher, Chia-Jung Busch
BACKGROUND: Recently enormous progress in cancer therapy has been achieved by the use of immune checkpoint inhibitors. Activating the body's own immune system has added a novel and powerful therapeutic option for the treatment of melanoma and lung cancer. Furthermore, the potential use of immunotherapy is being extensively explored also in other malignancies. OBJECTIVE OF REVIEW: This review summarizes current clinical studies using immune checkpoint modulators for the treatment of head and neck cancer (HNSCC)...
May 2, 2017: Clinical Otolaryngology
https://www.readbyqxmd.com/read/28419181/hyperprogression-during-anti-pd-1-pd-l1-therapy-in-patients-with-recurrent-and-or-metastatic-head-and-neck-squamous-cell-carcinoma
#14
E Saâda-Bouzid, C Defaucheux, A Karabajakian, V Palomar Coloma, V Servois, X Paoletti, C Even, J Fayette, J Guigay, D Loirat, F Peyrade, M Alt, J Gal, C Le Tourneau
Background: HASH(0x46ff5d0) Pembrolizumab and nivolumab are immune checkpoint inhibitors targeting PD-1 that have recently been approved in pretreated recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. In the clinic, some patients seem not only not to benefit from anti-PD-L1/PD-1 agents but rather to experience an acceleration of tumor growth kinetics (TGK). Patients and Methods: HASH(0x419f618) We retrospectively compared TGK on immunotherapy and TGK on last treatment in patients with R/M HNSCC treated with PD-1/PD-L1 inhibitors in four French centers...
April 13, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28382569/targeted-therapy-in-head-and-neck-cancer-an-update-on-current-clinical-developments-in-epidermal-growth-factor-receptor-targeted-therapy-and-immunotherapies
#15
REVIEW
Jonathan Moreira, Alexander Tobias, Michael P O'Brien, Mark Agulnik
Most patients diagnosed with head and neck squamous cell carcinoma (HNSCC) will present with locally advanced disease, requiring multimodality therapy. Despite this curative approach, a significant subset of these patients will develop locoregional failure and/or distant metastases. Despite significant progress in the treatment and subsequent prognosis of locally advanced HNSCC, the prognosis of those patients with recurrent and/or metastatic (R/M) HNSCC is poor, with short-lived responses to palliative chemotherapy and few therapeutic agents available...
May 2017: Drugs
https://www.readbyqxmd.com/read/28366274/pembrolizumab-in-advanced-head-and-neck-cancer
#16
Vicki Brower
No abstract text is available yet for this article.
March 30, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28328302/pembrolizumab-for-platinum-and-cetuximab-refractory-head-and-neck-cancer-results-from-a-single-arm-phase-ii-study
#17
Joshua Bauml, Tanguy Y Seiwert, David G Pfister, Francis Worden, Stephen V Liu, Jill Gilbert, Nabil F Saba, Jared Weiss, Lori Wirth, Ammar Sukari, Hyunseok Kang, Michael K Gibson, Erminia Massarelli, Steven Powell, Amy Meister, Xinxin Shu, Jonathan D Cheng, Robert Haddad
Purpose There are no approved treatments for recurrent/metastatic head and neck squamous cell carcinoma refractory to platinum and cetuximab. In the single-arm, phase II KEYNOTE-055 study, we evaluated pembrolizumab, an anti-programmed death 1 receptor antibody, in this platinum- and cetuximab-pretreated population with poor prognosis. Methods Eligibility stipulated disease progression within 6 months of platinum and cetuximab treatment. Patients received pembrolizumab 200 mg every 3 weeks. Imaging was performed every 6 to 9 weeks...
May 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28174141/checkpoint-inhibition-for-advanced-mucosal-melanoma
#18
Julia Thierauf, Johannes A Veit, Jochen Hess, Nicolai Treiber, Catharina Lisson, Stephanie E Weissinger, Martin Bommer, Thomas K Hoffmann
BACKGROUND: Whereas anti-PD-1 therapy has demonstrated a significant and durable response against advanced cutaneous melanoma, conventional chemotherapies have shown only minor benefit against advanced mucosal melanoma. OBJECTIVES: To investigate the efficacy of anti-PD-1 therapy in a small cohort of patients with mucosal melanoma of the head and neck. MATERIAL & METHODS: We analysed five patients with mucosal melanoma of the head and neck who received nivolumab or pembrolizumab, at an advanced stage...
February 3, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/28166090/chemotherapy-for-recurrent-metastatic-head-and-neck-cancers
#19
Andy Karabajakian, Philippe Toussaint, Eve-Marie Neidhardt, Valérie Paulus, Pierre Saintigny, Jérôme Fayette
Chemotherapy is the only option of treatment for most patients presenting with a recurrent and/or metastatic head and neck squamous cell carcinoma. The triple association of cisplatin, 5-fluorouracile, and cetuximab is still the current standard for fit patients. Other schemes are currently being compared with this protocol in ongoing trials and the association of cisplatin, docetaxel, and cetuximab appears to be the most efficient. The human papilloma virus is very likely a favorable prognostic factor. Immunotherapy with nivolumab or pembrolizumab is now a new standard of treatment in second line after yielding an improvement in overall survival, but predictive markers of efficacy are needed to refine the selection of patients...
April 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27895920/pd1-pd-l1-inhibition-as-a-potential-radiosensitizer-in-head-and-neck-squamous-cell-carcinoma-a-case-report
#20
Misako Nagasaka, Mark Zaki, Harold Kim, S Naweed Raza, George Yoo, Ho-Sheng Lin, Ammar Sukari
BACKGROUND: Immunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint inhibitors and anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently investigated. CASE PRESENTATION: We report a case of locally relapsed non-resectable oral cavity squamous cell carcinoma, with excellent local control after pembrolizumab (MK3475) followed by radiotherapy...
2016: Journal for Immunotherapy of Cancer
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