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"nivolumab" and "ipilimumab"

Pol Specenier
The treatment of melanoma is evolving rapidly over the past few years. Areas covered: We conducted a comprehensive review of the literature on the role of nivolumab in melanoma Expert commentary: Nivolumab is approved by FDA and EMA for the treatment of patients with metastatic melanoma. Nivolumab is superior to chemotherapy and to ipilimumab in previously untreated patients and to chemotherapy in ipilimumab pre-treated patients. The addition ipilimumab to nivolumab is associated with a higher response rate and a better PFS, particularly in patients with PD-L1 negative tumors, albeit at the cost of an increase in grade 3-4 adverse event rate...
October 25, 2016: Expert Review of Anticancer Therapy
C Franklin, E Livingstone, A Roesch, B Schilling, D Schadendorf
Malignant melanoma contributes the majority of skin cancer related deaths and shows an increasing incidence in the past years. Despite all efforts of early diagnosis, metastatic melanoma still has a poor prognosis and remains a challenge for treating physicians. In recent years, improved knowledge of the pathophysiology and a better understanding of the role of the immune system in tumour control have led to the development and approval of several immunotherapies. Monoclonal antibodies against different immune checkpoints have been revolutionizing the treatment of metastatic and unresectable melanoma...
September 2, 2016: European Journal of Surgical Oncology
Yang Yang, Jiaomiao Pei, Guozhen Gao, Zheng Yang, Shuzhong Guo, Bo Yue, Jianhua Qiu
We conducted a network meta-analysis in order to compare different strategies for managing melanoma patients. Electronic databases were searched for eligible randomized trials that compared different strategies in efficacy and tolerability. Five interventions were associated with a significant improvement in PFS over chemotherapy (all HR < 1): Ipilimumab, Tremelimumab, Nivolumab, Pembrolizumab 2 mg/kg and Ipilimumab + Nivolumab. Three interventions exhibited significantly improved OS results over chemotherapy (all HR < 1): Ipilimumab, Nivolumab and Ipilimumab + Chemotherapy...
October 13, 2016: Oncotarget
Young Kwang Chae, Lauren Chiec, Nisha Mohindra, Ryan Gentzler, Jyoti Patel, Francis Giles
Immune checkpoint inhibitors such as pembrolizumab, ipilimumab, and nivolumab, now FDA-approved for use in treating several types of cancer, have been associated with immune-related adverse effects. Specifically, the antibodies targeting the programmed-cell death-1 immune checkpoint, pembrolizumab and nivolumab, have been rarely reported to induce the development of type 1 diabetes mellitus. Here we describe a case of a patient who developed antibody-positive type 1 diabetes mellitus following treatment with pembrolizumab in combination with systemic chemotherapy for metastatic adenocarcinoma of the lung...
October 19, 2016: Cancer Immunology, Immunotherapy: CII
Xi Zhang, Yuge Ran, Kunjie Wang, Yuanxue Zhu, Jinghua Li
PURPOSE: Anti-programmed cell death receptor-1 (PD-1) antibodies have demonstrated antitumor activity in many cancer entities. Hepatic adverse events (AEs) are one of its major side effects, but the overall risks have not been systematically evaluated. Thus, we conducted this meta-analysis to investigate the overall incidence and risk of developing hepatic AEs in cancer patients treated with PD-1 inhibitors. METHODS: PubMed, Embase, and oncology conference proceedings were searched for relevant studies...
2016: Drug Design, Development and Therapy
Yuh-Min Chen
Immune checkpoint inhibition with blocking antibodies that target cytotoxic T-lymphocyte antigen-4 (CTLA-4) and the programmed cell death protein 1 (PD-1) pathway [PD-1/programmed death-ligand 1 (PD-L1)] have demonstrated promise in a variety of malignancies. While ipilimumab has been approved as a CTLA-4 blocking antibody by the US Food and Drug Administration for the treatment of advanced melanoma, it is still not approved for lung cancer treatment. In contrast, nivolumab and pembrolizumab, both PD-1 blocking antibodies, have been approved for second-line treatment of nonsmall cell lung cancer in 2015 because of their high potency and long-lasting effects in some patient subgroups...
September 29, 2016: Journal of the Chinese Medical Association: JCMA
Katy K Tsai, Miguel H Pampaloni, Charity Hope, Alain P Algazi, Britt-Marie Ljung, Laura Pincus, Adil I Daud
BACKGROUND: Antibodies against programmed death 1 (PD-1) receptor and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have transformed the systemic treatment of melanoma and many other cancers. Understanding the spectrum of benign findings and atypical response patterns seen in immune checkpoint blockade is important for accurately assessing treatment response as these immunotherapies become more widely used. CASE PRESENTATION: We report a 63-year-old man with metastatic melanoma successfully treated with combination CTLA-4 and PD-1 blockade (ipilimumab and nivolumab), after non-response to pembrolizumab monotherapy...
2016: Journal for Immunotherapy of Cancer
Emily de Golian, Bernice Y Kwong, Susan M Swetter, Silvina B Pugliese
The landscape of advanced and metastatic melanoma therapy has shifted dramatically in recent years. Since 2011, eight drugs (ipilimumab, vemurafenib, dabrafenib, trametinib, cometinib, pembrolizumab, nivolumab, and talimogene laherparepvec) have received FDA approval for the treatment of advanced or metastatic melanoma, including combination regimens of both small molecule kinase and immune checkpoint inhibitors. These therapies have revolutionized the management of unresectable regional nodal and distant melanoma, providing hope of extended survival to patients...
November 2016: Current Treatment Options in Oncology
Alina Basnet, Nibal Saad, Sam Benjamin
BACKGROUND: Melanoma is among the top three cancers to present with brain metastasis. The risk of brain metastases in advanced melanoma increases with disease duration. Cytotoxic chemotherapy does not have a significant role in the management of melanoma patients with brain metastases, neither alone nor in conjunction with radiation therapy. PATIENTS AND METHODS: We herein discuss a case of a 66-year-old male diagnosed initially with stage III-B melanoma and underwent a wide local excision with a split thickness graft and sentinel lymph node biopsy, followed by adjuvant treatment with high-dose interferon...
September 2016: Anticancer Research
G Santabarbara, P Maione, A Rossi, G Palazzolo, C Gridelli
INTRODUCTION: 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...
September 23, 2016: Expert Review of Clinical Pharmacology
F Stephen Hodi, Jason Chesney, Anna C Pavlick, Caroline Robert, Kenneth F Grossmann, David F McDermott, Gerald P Linette, Nicolas Meyer, Jeffrey K Giguere, Sanjiv S Agarwala, Montaser Shaheen, Marc S Ernstoff, David R Minor, April K Salama, Matthew H Taylor, Patrick A Ott, Christine Horak, Paul Gagnier, Joel Jiang, Jedd D Wolchok, Michael A Postow
BACKGROUND: Results from phase 2 and 3 trials in patients with advanced melanoma have shown significant improvements in the proportion of patients achieving an objective response and prolonged progression-free survival with the combination of nivolumab (an anti-PD-1 antibody) plus ipilimumab (an anti-CTLA-4 antibody) compared with ipilimumab alone. We report 2-year overall survival data from a randomised controlled trial assessing this treatment in previously untreated advanced melanoma...
September 9, 2016: Lancet Oncology
Jessica C Hassel
No abstract text is available yet for this article.
September 8, 2016: Lancet Oncology
Saskia Herz, Thomas Höfer, Matina Papapanagiotou, Julia Christina Leyh, Sarah Meyenburg, Dirk Schadendorf, Selma Ugurel, Alexander Roesch, Elisabeth Livingstone, Bastian Schilling, Cindy Franklin
BACKGROUND: Immune-checkpoint inhibitors have been approved for the treatment of metastatic melanoma based on several phase III trials. Patients after organ transplantation and patients with impaired renal function were excluded from these studies. Recently, allograft rejections were reported in organ transplant recipients receiving PD-1 blocking antibodies. PATIENTS AND FINDINGS: Four patients with metastatic melanoma and impaired kidney function (baseline serum creatinine 1...
November 2016: European Journal of Cancer
Mark J Selby, John J Engelhardt, Robert J Johnston, Li-Sheng Lu, Minhua Han, Kent Thudium, Dapeng Yao, Michael Quigley, Jose Valle, Changyu Wang, Bing Chen, Pina M Cardarelli, Diann Blanset, Alan J Korman
The monoclonal antibodies ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) have shown remarkable antitumor activity in an increasing number of cancers. When combined, ipilimumab and nivolumab have demonstrated superior activity in patients with metastatic melanoma (CHECKMATE-067). Here we describe the preclinical development strategy that predicted these clinical results. Synergistic antitumor activity in mouse MC38 and CT26 colorectal tumor models was observed with concurrent, but not sequential CTLA-4 and PD-1 blockade...
2016: PloS One
Elia Moreno-Cubero, Juan-Ramón Larrubia
Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8(+) T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment...
July 28, 2016: World Journal of Gastroenterology: WJG
Paolo A Ascierto, Vito Vanella, Antonio Maria Grimaldi, Festino Lucia, Marco Palla, Ester Simeone, Nicola Mozzillo
The anti-PD-1 agent, nivolumab, has been approved both as monotherapy and in combination with ipilimumab for the treatment of unresectable or metastatic melanoma in the USA and European Union. Here we present the case of a patient with treatment-naive, metastatic mucosal melanoma and baseline LDH approximately seven times the upper limit of normal. The patient was enrolled in a clinical trial (CheckMate 066) and achieved a partial response, followed by a durable complete response with nivolumab treatment. The patient's LDH levels were documented in each cycle and dropped markedly within 2 months, when partial response to treatment was already evident...
September 7, 2016: Cancer Immunology, Immunotherapy: CII
Carrie Luu, Nikhil I Khushalani, Jonathan S Zager
INTRODUCTION: Immunotherapy has revolutionized the treatment of metastatic melanoma and dramatically improved patient outcomes. Ipilimumab, an inhibitor of cytotoxic T-lymphocyte antigen-4 (CTLA-4), was the first immunotherapeutic agent to demonstrate improved survival in advanced melanoma. More recently, other immune checkpoint inhibitors, including the programmed death-1 (PD-1) inhibitors pembrolizumab and nivolumab, have demonstrated efficacy in locally advanced unresectable and metastatic melanoma...
September 20, 2016: Expert Opinion on Biological Therapy
Belal Firwana, Rahul Ravilla, Mihir Raval, Laura Hutchins, Fade Mahmoud
Immunotherapy with checkpoint inhibitors has revolutionized the management of metastatic melanoma. These checkpoints, namely the cytotoxic T lymphocyte antigen 4 and the programmed T cell death 1 receptor, possess an inhibitory effect on the T cell function. Pharmacologic inhibition of cytotoxic T lymphocyte antigen 4 with ipilimumab and programmed T cell death 1 with either pembrolizumab or nivolumab has resulted in long-term sustained responses among patients with metastatic melanoma. The adverse events of these medications are predominantly immune related...
September 2, 2016: Journal of Oncology Pharmacy Practice
Helena Linardou, Helen Gogas
Checkpoint inhibitors have revolutionized the treatment of patients with metastatic melanoma offering improved responses and significant survival benefit. These agents are now approved for the treatment of metastatic melanoma, squamous and non-squamous non-small cell lung cancer (NSCLC) and kidney cancer, while they are now being investigated in a range of other malignancies. In addition, another anti-PD-L1 monoclonal antibody (atezolizumab) was recently approved for urothelial cancer. Ipilimumab, an anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody and the anti-PD-1 agents nivolumab and pembrolizumab have followed large clinical development programs, therefore, information regarding their safety and toxicity profile is readily available...
July 2016: Annals of Translational Medicine
James W T Toh, Paul de Souza, Stephanie H Lim, Puneet Singh, Wei Chua, Weng Ng, Kevin J Spring
Colorectal cancers (CRCs) have been identified as potential targets for immunotherapy with programmed cell death (PD)-1 inhibitors. English-language publications from MedLine and Embase that evaluated PD-1/PD ligand 1 (PD-L1) in the CRC tumor microenvironment and clinical trials that assessed PD-1 inhibitors were included. Sixteen abstracts were screened. Fifteen met the inclusion criteria. After review of the full texts, this resulted in a final reference list of 8 studies eligible for review. Five studies that assessed PD-1/PD-L1 in CRC and 3 trials that assessed PD-1 inhibitors were included...
July 22, 2016: Clinical Colorectal Cancer
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