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https://www.readbyqxmd.com/read/28512504/a-case-report-of-drug-induced-myopathy-involving-extraocular-muscles-after-combination-therapy-with-tremelimumab-and-durvalumab-for-non-small-cell-lung-cancer
#1
William Carrera, Brandon J Baartman, Gregory Kosmorsky
Recently developed anti-tumour therapies targeting immune checkpoints include tremelimumab and durvalumab. These agents have incompletely characterised side effect profiles. The authors report a 68-year-old man treated for non-small cell lung cancer (NSCLC) with a combination of tremelimumab and durvalumab. After treatment he developed diplopia, ptosis, fatigue, weakness, and an inflammatory myopathy affecting the extraocular muscles requiring hospitalisation. Electromyography (EMG) testing and muscle biopsy suggested inflammatory myopathy without sign of myasthenia...
June 2017: Neuro-ophthalmology
https://www.readbyqxmd.com/read/28499515/incidence-of-pneumonitis-with-use-of-pd-1-and-pd-l1-inhibitors-in-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis-of-trials
#2
Monica Khunger, Sagar Rakshit, Vinay Pasupuleti, Adrian V Hernandez, Peter Mazzone, James Stevenson, Nathan A Pennell, Vamsidhar Velcheti
BACKGROUND: PD-1/PD-L1 inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis, and differences according to type of inhibitors and prior chemotherapy use. METHODS: Medline, Embase and Scopus databases were searched up to November 2016...
May 9, 2017: Chest
https://www.readbyqxmd.com/read/28493171/immunotherapy-in-urothelial-cancer-recent-results-and-future-perspectives
#3
REVIEW
Matthew S Farina, Kevin T Lundgren, Joaquim Bellmunt
Cytotoxic chemotherapy has been the only systemic treatment of locally advanced and metastatic urothelial carcinoma for decades. Long-term survival remains stagnant around 12-14 months for patients with advanced disease who have progressed on or recurred after receiving first-line platinum-based chemotherapy. Improving clinical outcomes for patients with urothelial carcinoma in all disease settings requires the development of novel treatments, especially for patients who failed on first-line chemotherapy. Since the discovery of intravesical Bacillus-Calmette Guerin (BCG) in the 1970s for non-muscle invasive disease, there have not been any major breakthrough drugs that exploit the immune-sensitivity of bladder cancer until recently...
May 11, 2017: Drugs
https://www.readbyqxmd.com/read/28471727/safety-and-clinical-activity-of-the-programmed-death-ligand-1-inhibitor-durvalumab-in-combination-with-poly-adp-ribose-polymerase-inhibitor-olaparib-or-vascular-endothelial-growth-factor-receptor-1-3-inhibitor-cediranib-in-women-s-cancers-a-dose-escalation
#4
Jung-Min Lee, Ashley Cimino-Mathews, Cody J Peer, Alexandra Zimmer, Stanley Lipkowitz, Christina M Annunziata, Liang Cao, Maria I Harrell, Elizabeth M Swisher, Nicole Houston, Dana-Adriana Botesteanu, Janis M Taube, Elizabeth Thompson, Aleksandra Ogurtsova, Haiying Xu, Jeffers Nguyen, Tony W Ho, William D Figg, Elise C Kohn
Purpose Data suggest that DNA damage by poly (ADP-ribose) polymerase inhibition and/or reduced vascular endothelial growth factor signaling by vascular endothelial growth factor receptor inhibition may complement antitumor activity of immune checkpoint blockade. We hypothesize the programmed death-ligand 1 (PD-L1) inhibitor, durvalumab, olaparib, or cediranib combinations are tolerable and active in recurrent women's cancers. Patients and Methods This phase I study tested durvalumab doublets in parallel 3 + 3 dose escalations...
May 4, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28466250/outcomes-targeting-the-pd-1-pd-l1-axis-in-conjunction-with-stereotactic-radiation-for-patients-with-non-small-cell-lung-cancer-brain-metastases
#5
Kamran A Ahmed, Sungjune Kim, John Arrington, Arash O Naghavi, Thomas J Dilling, Ben C Creelan, Scott J Antonia, Jimmy J Caudell, Louis B Harrison, Solmaz Sahebjam, Jhanelle E Gray, Arnold B Etame, Peter A Johnstone, Michael Yu, Bradford A Perez
Anti-PD-1/PD-L1 therapies have demonstrated activity in patients with advanced stage non-small cell lung cancer (NSCLC). However, little is known about the safety and feasibility of patients receiving anti-PD-1/PD-L1 therapy and stereotactic radiation for the treatment of brain metastases. Data were analyzed retrospectively from NSCLC patients treated with stereotactic radiation either before, during or after anti-PD-1/PD-L1 therapy with nivolumab (anti-PD-1) or durvalumab (anti-PD-L1). Seventeen patients treated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiation therapy (FSRT) to 49 brain metastases over 21 sessions were identified...
May 2, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28403786/immune-checkpoint-inhibitors-and-cardiac-toxicity-an-emerging-issue
#6
Gilda Varricchi, Giancarlo Marone, Valentina Mercurio, Maria Rosaria Galdiero, Domenico Bonaduce, Carlo G Tocchetti
Although survival of patients with different types of cancer has improved, cardiotoxicity induced by anti-neoplastic drugs remains a critical issue. Cardiac dysfunction after treatment with anthracyclines has historically been a major problem. However, also targeted therapies and biological molecules can induce reversible and irreversible cardiac dysfunction. Cancer immunotherapies over the last years have revolutionized the clinical management of a wide spectrum of solid and hematopoietic malignancies previously endowed with poor prognosis...
April 7, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28271729/egfr-tki-combination-with-immunotherapy-in-non-small-cell-lung-cancer
#7
REVIEW
Myung-Ju Ahn, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) has significantly improved clinical outcomes compared with chemotherapy in non-small cell lung cancer (NSCLC) patients with sensitizing EGFR gene mutation. Areas covered: Almost all patients treated with EGFR TKIs eventually develop acquired resistance. It has been reported that activation of the oncogenic EGFR pathway enhances susceptibility of the lung tumors to PD-1 blockade in mouse model, suggesting combination of PD1 blockade with EGFR TKIs may be a promising therapeutic strategy...
April 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28271259/neoadjuvant-treatment-for-locally-invasive-esophageal-cancer
#8
Wade T Iams, Victoria M Villaflor
Locally advanced esophageal carcinoma has a poor prognosis, and epidemiologic trends show that more patients are being diagnosed with locally advanced esophageal carcinoma and with adenocarcinoma histology. This prompts a review and evaluation of the field regarding standard of care treatment for patients with locally advanced esophageal carcinoma, both adenocarcinoma and squamous cell carcinoma. We review the evidence showing the moderate benefit of neoadjuvant chemoradiation followed by esophagectomy compared to perioperative chemotherapy plus esophagectomy in patients who are good operative candidates...
March 7, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/28214651/a-review-on-the-evolution-of-pd-1-pd-l1-immunotherapy-for-bladder-cancer-the-future-is-now
#9
REVIEW
Joaquin Bellmunt, Thomas Powles, Nicholas J Vogelzang
The treatment of bladder cancer has evolved over time to encompass not only the traditional modalities of chemotherapy and surgery, but has been particularly impacted by the use of immunotherapy. The first immunotherapy was the live, attenuated bacterial Bacillus Calmette-Guérin vaccine, which has been the standard of care non-muscle-invasive bladder cancer since 1990. Modern immunotherapy has focused on inhibitors of checkpoint proteins, which are molecules that impede immune function, thereby allowing tumor cells to grow and proliferate unregulated...
March 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#10
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28073845/agreement-between-programmed-cell-death-ligand-1-diagnostic-assays-across-multiple-protein-expression-cut-offs-in-non-small-cell-lung-cancer
#11
Marianne J Ratcliffe, Alan Sharpe, Anita Midha, Craig Barker, Marietta Scott, Paul Scorer, Hytham Al-Masri, Marlon Rebelatto, Jill Walker
PURPOSE: agents:Immunotherapies targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) demonstrate encouraging antitumor activity and manageable tolerability in non-small cell lung cancer (NSCLC), especially in patients with high tumor PD-L1 expression, as detected by companion or complementary diagnostic assays developed for individual agents. A laboratory is unlikely to use multiple assay platforms. Furthermore, commercially available diagnostic assays are not standardized and different assay methods could lead to inappropriate treatment selection...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28064556/pd-1-checkpoint-blockade-alone-or-combined-pd-1-and-ctla-4-blockade-as-immunotherapy-for-lung-cancer
#12
Tawee Tanvetyanon, Jhanelle E Gray, Scott J Antonia
Signaling through T-cell surface, an immune checkpoint protein such as PD-1 or CTLA-4 helps dampen or terminate unwanted immune responses. Blocking a single immune checkpoint or multiple checkpoints simultaneously can generate anti-tumor activity against a variety of cancers including lung cancer. Area covered: This review highlights the results of recent clinical studies of single or combination checkpoint inhibitor immunotherapy in non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). The authors discuss pembrolizumab and pembrolizumab plus ipilimumab, durvalumab and durvalumab plus tremelimumab, nivolumab and nivolumab plus ipilimumab for NSCLC as well as nivolumab and nivolumab plus ipilimumab for SCLC...
March 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/27960628/antibodies-to-watch-in-2017
#13
Janice M Reichert
Over 50 investigational monoclonal antibody (mAb) therapeutics are currently undergoing evaluation in late-stage clinical studies, which is expected to drive a trend toward first marketing approvals of at least 6-9 mAbs per year in the near-term. In the United States (US), a total of 6 and 9 mAbs were granted first approvals during 2014 and 2015, respectively; all these products are also approved in the European Union (EU). As of December 1, 2016, 6 mAbs (atezolizumab, olaratumab, reslizumab, ixekizumab, bezlotoxumab, oblitoxaximab) had been granted first approvals during 2016 in either the EU or US...
February 2017: MAbs
https://www.readbyqxmd.com/read/27764686/concurrent-irradiation-with-the-anti-programmed-cell-death-ligand-1-immune-checkpoint-blocker-durvalumab-single-centre-subset-analysis-from-a-phase-1-2-trial
#14
Antonin Levy, Christophe Massard, Jean-Charles Soria, Eric Deutsch
PURPOSE: To assess preliminary safety and efficacy results of the anti-programmed cell death ligand-1 (anti-PD-L1) durvalumab in combination with radiotherapy (RT) in an expansion cohort of patients included in a phase 1/2 trial at our institution. PATIENTS AND METHODS: Data from patients who received concurrent palliative RT with durvalumab (10 mg/kg every 2 weeks via intravenous infusion) were analysed in terms of safety (CTCAE v4.0) and efficacy (RECIST v1.1 and tumour growth rate [TGR])...
November 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27717372/development-of-a-programmed-cell-death-ligand-1-immunohistochemical-assay-validated-for-analysis-of-non-small-cell-lung-cancer-and-head-and-neck-squamous-cell-carcinoma
#15
MULTICENTER STUDY
Marlon C Rebelatto, Anita Midha, Amita Mistry, Constantine Sabalos, Nicole Schechter, Xia Li, Xiaoping Jin, Keith E Steele, Paul B Robbins, John A Blake-Haskins, Jill Walker
BACKGROUND: A high-quality programmed cell-death ligand 1 (PD-L1) diagnostic assay may help predict which patients are more likely to respond to anti-programmed cell death-1 (PD-1)/PD-L1 antibody-based cancer therapy. Here we describe a PD-L1 immunohistochemical (IHC) staining protocol developed by Ventana Medical Systems Inc. and key analytical parameters of its use in formalin-fixed, paraffin-embedded (FFPE) samples of non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC)...
October 8, 2016: Diagnostic Pathology
https://www.readbyqxmd.com/read/27623999/novel-immunotherapy-in-the-treatment-of-advanced-non-small-cell-lung-cancer
#16
REVIEW
G Santabarbara, P Maione, A Rossi, G Palazzolo, C Gridelli
Lung cancers remain the principal cause of death cancer-related worldwide with a poor survival rate at five years from diagnosis. In patients with NSCLC harboring specific genetic alterations the anti EGFR TKIs and the ALK TKIs have improved the response rate and the quality of life compared to standard platinum-based chemotherapy. New approaches possibly applicable at the major of patients are needed. Areas covered: The discovery that the immune system plays a fundamental role in the fight against cancer. The cancer cells use mechanisms able to avoid the immune control has led to the development of drugs able to overcome this escape route...
December 2016: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27532023/pd-l1-biomarker-testing-for-non-small-cell-lung-cancer-truth-or-fiction
#17
REVIEW
Claud Grigg, Naiyer A Rizvi
Research in cancer immunology is currently accelerating following a series of cancer immunotherapy breakthroughs during the last 5 years. Various monoclonal antibodies which block the interaction between checkpoint molecules PD-1 on immune cells and PD-L1 on cancer cells have been used to successfully treat non-small cell lung cancer (NSCLC), including some durable responses lasting years. Two drugs, nivolumab and pembrolizumab, are now FDA approved for use in certain patients who have failed or progressed on platinum-based or targeted therapies while agents targeting PD-L1, atezolizumab and durvalumab, are approaching the final stages of clinical testing...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27389724/battling-regional-stage-iii-lung-cancer-bumpy-road-of-a-cancer-survivor-in-the-immunotherapy-age
#18
Zhonglin Hao, Paul Biddinger, Carsten Schroeder, Khurram Tariq
A 58-year-old woman, a heavy smoker, was diagnosed with stage III squamous cell lung cancer. She was treated with concurrent chemotherapy and radiotherapy, with partial response. 2 months later, she had haemoptysis caused by brisk bleeding from the radiated right upper lobe. Fortunately, her bleed was self-limited. 4 months later, a rapidly enlarging renal mass was discovered and turned out to be metastatic from the lung primary. Second-line chemotherapy with docetaxel and ramucirumab did not have effects on the renal mass after 2 cycles...
July 7, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27321156/anti-pd-l1-inhibitor-durvalumab-in-bladder-cancer
#19
Vicki Brower
No abstract text is available yet for this article.
July 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27269937/safety-and-efficacy-of-durvalumab-medi4736-an-anti-programmed-cell-death-ligand-1-immune-checkpoint-inhibitor-in-patients-with-advanced-urothelial-bladder-cancer
#20
Christophe Massard, Michael S Gordon, Sunil Sharma, Saeed Rafii, Zev A Wainberg, Jason Luke, Tyler J Curiel, Gerardo Colon-Otero, Omid Hamid, Rachel E Sanborn, Peter H O'Donnell, Alexandra Drakaki, Winston Tan, John F Kurland, Marlon C Rebelatto, Xiaoping Jin, John A Blake-Haskins, Ashok Gupta, Neil H Segal
PURPOSE: To investigate the safety and efficacy of durvalumab, a human monoclonal antibody that binds programmed cell death ligand-1 (PD-L1), and the role of PD-L1 expression on clinical response in patients with advanced urothelial bladder cancer (UBC). METHODS: A phase 1/2 multicenter, open-label study is being conducted in patients with inoperable or metastatic solid tumors. We report here the results from the UBC expansion cohort. Durvalumab (MEDI4736, 10 mg/kg every 2 weeks) was administered intravenously for up to 12 months...
September 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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