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https://www.readbyqxmd.com/read/29432222/immunotherapy-for-recurrent-metastatic-head-and-neck-cancer
#1
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...
February 8, 2018: Current Opinion in Otolaryngology & Head and Neck Surgery
https://www.readbyqxmd.com/read/29416316/durvalumab-an-investigational-anti-pd-l1-monoclonal-antibody-for-the-treatment-of-urothelial-carcinoma
#2
REVIEW
Izak Faiena, Amy L Cummings, Anna M Crosetti, Allan J Pantuck, Karim Chamie, Alexandra Drakaki
Our expanding knowledge of immunotherapy for solid tumors has led to an explosion of clinical trials aimed at urothelial carcinoma. The primary strategy is centered on unleashing the immune system by releasing the inhibitory signals propagated by programmed cell death-1 (PD-1) and its ligand programmed cell death ligand-1 (PD-L1). Many antibody constructs have been developed to block these interactions and are used in clinical trials. The Food and Drug Administration has already approved a number of checkpoint inhibitors such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibodies including ipilimumab; anti-PD-1 monoclonal antibodies including nivolumab and pembrolizumab; anti-PD-L1 antibodies including atezolizumab, avelumab, and durvalumab...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29374302/-durvalumab-improves-prognosis-of-stage%C3%A2-iii-non-small-cell-lung-cancer-after-definitive-chemoradiotherapy
#3
Markus Hecht, Udo S Gaipl, Rainer Fietkau
No abstract text is available yet for this article.
January 26, 2018: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/29370105/tackling-cancer-resistance-by-immunotherapy-updated-clinical-impact-and-safety-of-pd-1-pd-l1-inhibitors
#4
REVIEW
Shifaa M Abdin, Dana M Zaher, El-Shaimaa A Arafa, Hany A Omar
Cancer therapy has been constantly evolving with the hope of finding the most effective agents with the least toxic effects to eradicate tumors. Cancer immunotherapy is currently among the most promising options, fulfilling this hope in a wide range of tumors. Immunotherapy aims to activate immunity to fight cancer in a very specific and targeted manner; however, some abnormal immune reactions known as immune-related adverse events (IRAEs) might occur. Therefore, many researchers are aiming to define the most proper protocols for managing these complications without interfering with the anticancer effect...
January 25, 2018: Cancers
https://www.readbyqxmd.com/read/29358503/beyond-concurrent-chemoradiation-the-emerging-role-of-pd-1-pd-l1-inhibitors-in-stage-iii-lung-cancer
#5
Neal S McCall, Adam P Dicker, Bo Lu
Concurrent chemoradiation (cCRT) with platinum-based chemotherapy is standard of care therapy for patients with Stage III unresectable non-small cell lung cancer (NSCLC). Though potentially curative, five-year overall survival has hovered around 20%, despite extensive efforts to improve outcomes with increasing doses of conformal radiation and intensification of systemic therapy with either induction or consolidation chemotherapy. PD-1/PD-L1 immune checkpoint inhibitors have demonstrated unprecedented efficacy in patients with Stage IV NSCLC...
January 22, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29357560/re-safety-and-efficacy-of-durvalumab-medi4736-an-anti-programmed-cell-death-ligand-1-immune-checkpoint-inhibitor-in-patients-with-advanced-urothelial-bladder-cancer
#6
https://www.readbyqxmd.com/read/29355614/head-and-neck-squamous-cell-carcinoma-genomics-and-emerging-biomarkers-for-immunomodulatory-cancer-treatments
#7
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 17, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29303787/supportive-care-in-the-era-of-immunotherapies-for-advanced-non-small-cell-lung-cancer
#8
Gil Awada, Jean Klastersky
PURPOSE OF REVIEW: The therapeutic armamentarium for advanced non-small-cell lung cancer has evolved considerably over the past years. Immune checkpoint inhibitors targeting programmed cell death-1 such as pembrolizumab and nivolumab or programmed cell death ligand 1 such as atezolizumab, durvalumab and avelumab have shown favorable efficacy results in this patient population in the first-line and second-line setting. These immunotherapies are associated with a distinct toxicity profile based on autoimmune organ toxicity which is a new challenge for supportive care during treatment with these drugs...
January 4, 2018: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29299404/evaluation-of-rare-but-severe-immune-related-adverse-effects-in-pd-1-and-pd-l1-inhibitors-in-non-small-cell-lung-cancer-a-meta-analysis
#9
Yang-Bo Hu, Qun Zhang, Hui-Juan Li, Jean Maire Michot, Hong-Bing Liu, Ping Zhan, Tang-Feng Lv, Yong Song
Background: Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitor therapy is showing marked efficacy in advanced non-small cell lung cancer (NSCLC). Meanwhile, it is concomitant with distinctive immune-related adverse effects. We aim to describe the incidence of pneumonitis and other rare but severe immune-related adverse effects (IRAEs), as well as treatment related deaths. In addition, we analyze the differences in incidence of pneumonitis between PD-1 and PD-L1 inhibitors and standard-of-care chemotherapy...
December 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29285547/association-of-immunotherapy-with-durable-survival-as-defined-by-value-frameworks-for-cancer-care
#10
Omer Ben-Aharon, Racheli Magnezi, Moshe Leshno, Daniel A Goldstein
Importance: Modern immuno-oncology agents have generated great excitement because of their potential to provide durable survival for some patients. However, there is concern regarding the cost of cancer care, and multiple frameworks have been developed to assess value. The American Society of Clinical Oncology (ASCO) framework awards bonus points if substantial durable survival is demonstrated. Objective: To assess whether modern immuno-oncology agents reach defined efficacy thresholds in value frameworks...
December 28, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29276274/formulary-drug-review-naldemedine
#11
Danial E Baker
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers...
July 2017: Hospital Pharmacy
https://www.readbyqxmd.com/read/29243223/population-pharmacokinetics-of-durvalumab-in-cancer-patients-and-association-with-longitudinal-biomarkers-of-disease-status
#12
Paul G Baverel, Vincent F S Dubois, Chao Yu Jin, Yanan Zheng, Xuyang Song, Xiaoping Jin, Pralay Mukhopadhyay, Ashok Gupta, Phillip A Dennis, Yong Ben, Paolo Vicini, Lorin Roskos, Rajesh Narwal
The objectives of this analysis were to develop a population pharmacokinetics (PK) model of durvalumab, an anti-PD-L1 antibody, and quantify the impact of baseline and time-varying patient/disease characteristics on PK. Pooled data from two studies (1,409 patients providing 7,407 PK samples) were analysed with non-linear mixed effects modelling. Durvalumab PK was best described by a 2-compartment model with both linear and non-linear clearances. Three candidate models were evaluated: a time-invariant CL model, an empirical time-varying CL model, and a semi-mechanistic time-varying CL model incorporating longitudinal covariates related to disease status (tumor shrinkage and albumin)...
December 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29243222/population-modeling-of-tumor-kinetics-and-overall-survival-to-identify-prognostic-and-predictive-biomarkers-of-efficacy-for-durvalumab-in-patients-with-urothelial-carcinoma
#13
Yanan Zheng, Rajesh Narwal, ChaoYu Jin, Paul G Baverel, Xiaoping Jin, Ashok Gupta, Yong Ben, Bing Wang, Pralay Mukhopadhyay, Brandon W Higgs, Lorin Roskos
Durvalumab is an anti-PD-L1 monoclonal antibody approved for patients with locally advanced or metastatic urothelial carcinoma (UC) that has progressed after platinum-containing chemotherapy. A population tumor kinetic model, coupled with dropout and survival models, was developed to describe longitudinal tumor size data and predict overall survival in UC patients treated with durvalumab (NCT01693562) and to identify prognostic and predictive biomarkers of clinical outcomes. Model-based covariate analysis identified liver metastasis as the most influential factor for tumor growth and immune-cell PD-L1 expression and baseline tumor burden as predictive factors for tumor killing...
December 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29239189/-immunotherapy-in-the-treatment-of-lung-cancer
#14
O Fiala, O Šorejs, M Pešek, J Fínek
BACKGROUND: Lung cancer occupies the leading position of cancer incidence and mortality worldwide, including in the Czech Republic. Despite significant advances in systemic oncology treatments, lung cancer still has the worst prognosis, which is driving the need for innovative therapies and methods to treat this disease. Immunotherapy is a developing area of systemic oncology treatment, which has recently begun to be significantly applied to patients with lung carcinoma. The most useful type of immunotherapy currently employs checkpoint inhibitors, including CTLA-4 inhibitors (ipilimumab and tremelimumab) and PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, durvalumab, and avelumab)...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29239187/-immunotherapy-for-bladder-cancer
#15
T Büchler
Urothelial carcinoma is the most common urological malignancy. Nonspecific immunotherapy using the Bacillus Calmette-Guerin vaccine has long been the mainstay for the treatment of high-risk superficial bladder carcinoma in an adjuvant setting after transurethral endoscopic resection. In metastatic disease, cisplatin-based chemotherapy remains the main therapeutic modality. In Europe, the standard second-line chemotherapy for patients with cisplatin-refractory tumours is vinflunine. Other systemic treatments with a lower level of evidence include paclitaxel and docetaxel...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29205200/immunotherapy-in-metastatic-urothelial-carcinoma-focus-on-immune-checkpoint-inhibition
#16
REVIEW
Arlene Siefker-Radtke, Brendan Curti
Immunotherapy has been used in localized urothelial carcinoma for decades, especially in the treatment of superficial disease, in which instillation of BCG is a commonly used treatment option. Clinical investigations based on new insights into the immunogenic potential of metastatic urothelial carcinoma have led to the accelerated FDA approval of the immune checkpoint inhibitors atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab. Preliminary findings suggest additional benefits of combinations of immunotherapeutic agents as a future treatment approach in metastatic urothelial carcinoma...
December 5, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29191596/pd-l1-expression-in-advanced-nsclc-insights-into-risk-stratification-and-treatment-selection-from-a-systematic-literature-review
#17
REVIEW
Robert Brody, Yiduo Zhang, Marc Ballas, Mohd Kashif Siddiqui, Palvi Gupta, Craig Barker, Anita Midha, Jill Walker
Tumors can evade immune detection by exploiting inhibitory immune checkpoints such as the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway. Antibodies that block this pathway offer a promising new approach to treatment in advanced/metastatic non-small cell lung cancer (NSCLC). A systematic review of the literature was conducted to assess the association of PD-L1 with important patient and disease characteristics, the prognostic significance of PD-L1 expressing NSCLC tumors, and the value of PD-L1 as a predictive biomarker of response to anti-PD-1/PD-L1 treatments in advanced/metastatic NSCLC...
October 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29175147/durvalumab-boosts-progression-free-survival-in-nsclc
#18
Elizabeth Gourd
No abstract text is available yet for this article.
November 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29157296/biomarkers-for-immunotherapy-in-bladder-cancer-a-moving-target
#19
REVIEW
David H Aggen, Charles G Drake
Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29140105/durvalumab-in-non-small-cell-lung-cancer-patients-current-developments
#20
Laura Mezquita, David Planchard
Immune checkpoint inhibitors (ICIs) are a key component of treating advanced cancer patients, principally antibodies against CTLA-4 and PD-1 or PD-L1. Durvalumab (MEDI4736) is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1, which binds to PD-1 and CD80, but not to PD-L2. Single-agent durvalumab showed clinical efficacy and a manageable safety profile in advanced non-small-cell lung cancer, particularly the ≥25% PD-L1+ population. Durvalumab is under evaluation in early, locally advanced and advanced disease as monotherapy and combined with ICIs, targeted therapies, chemotherapy and radiotherapy...
November 15, 2017: Future Oncology
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