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Emily B Tsai, Kelsey Pomykala, Kathleen Ruchalski, Scott Genshaft, Fereidoun Abtin, Antonio Gutierrez, Hyun J Kim, Alice Li, Carlos Adame, Ashkan Jalalian, Brian Wolf, Edward B Garon, Jonathan W Goldman, Robert Suh
Purpose To determine feasibility and safety of biopsy and repeat biopsy for assessment of programmed cell death ligand-1 (PD-L1) status. Materials and Methods This retrospective analysis reviewed 101 patients who underwent transthoracic core needle biopsy for the KEYNOTE-001 (MK-3475) clinical trial of pembrolizumab, an antiprogrammed cell death-1 therapy for non-small cell lung cancer, from May 2012 to September 2014. Sixty-one male patients (mean age, 66.1 years; range 36-83 years) and 40 female patients (mean age, 66...
December 12, 2017: Radiology
Romualdo Barroso-Sousa, William T Barry, Ana C Garrido-Castro, F Stephen Hodi, Le Min, Ian E Krop, Sara M Tolaney
Importance: If not promptly recognized, endocrine dysfunction can be life threatening. The incidence and risk of developing such adverse events (AEs) following the use of immune checkpoint inhibitor (ICI) regimens are unknown. Objective: To compare the incidence and risk of endocrine AEs following treatment with US Food and Drug Administration-approved ICI regimens. Data Sources: A PubMed search through July 18, 2016, using the following keywords was performed: "ipilimumab," "MDX-010," "nivolumab," "BMS-963558," "pembrolizumab," "MK-3475," "atezolizumab," "MPDL3280A," and "phase...
September 28, 2017: JAMA Oncology
Anthony W Tolcher, Mario Sznol, Siwen Hu-Lieskovan, Kyriakos P Papadopoulos, Amita Patnaik, Drew W Rasco, Donna Di Gravio, Bo Huang, Dhiraj Gambhire, Ying Chen, Aron D Thall, Nuzhat Pathan, Emmett V Schmidt, Laura Q M Chow
Purpose: This phase Ib study (NCT02179918) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of utomilumab, a fully human IgG2 mAb agonist of the T-cell costimulatory receptor 4-1BB/CD137 in combination with the humanized, PD-1-blocking IgG4 mAb pembrolizumab in patients with advanced solid tumors.Experimental Design: Utomilumab (0.45-5.0 mg/kg) and pembrolizumab (2 mg/kg) were administered intravenously every 3 weeks. Utomilumab dose escalation was conducted using the time-to-event continual reassessment method...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the leading killer of both men and women in the US, and the 5-year survival remains poor. However, the approval of checkpoint blockade immunotherapy has shifted the treatment paradigm and provides hope for improved survival. The ability of non-small-cell lung cancer (NSCLC) to evade the host immune system can be overcome by agents such as pembrolizumab (MK-3475/lambrolizumab), which is a monoclonal antibody targeting the programmed death 1 (PD-1) receptor. In early studies, treatment with pembrolizumab led to dramatic and durable responses in select patients (PD-L1+ tumors)...
2017: Lung Cancer: Targets and Therapy
Naoya Yamazaki, Tatsuya Takenouchi, Manabu Fujimoto, Hironobu Ihn, Hiroshi Uchi, Takashi Inozume, Yoshio Kiyohara, Hisashi Uhara, Kazuhiko Nakagawa, Hiroshi Furukawa, Hidefumi Wada, Kazuo Noguchi, Takashi Shimamoto, Kenji Yokota
PURPOSE: This phase I b study evaluated the safety and anti-tumor activity of pembrolizumab in Japanese patients with advanced melanoma. METHODS: Pembrolizumab (2 mg/kg) was given every 3 weeks (Q3W) for up to 2 years or until confirmed progression or unacceptable toxicity. The tumor response was assessed as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by both investigator review and central review. RESULTS: Forty-two patients with advanced melanoma received pembrolizumab...
April 2017: Cancer Chemotherapy and Pharmacology
Gregory S Alexander, Joshua D Palmer, Madalina Tuluc, Jianqing Lin, Adam P Dicker, Voichita Bar-Ad, Larry A Harshyne, Jennifer Louie, Colette M Shaw, D Craig Hooper, Bo Lu
BACKGROUND: Pembrolizumab is a monoclonal antibody that is designed against programmed cell death protein 1 (PD-1). Pembrolizumab and other immunocheckpoint-blocking monoclonal antibodies work by modulating a patient's own immune system to increase anti-tumor activity. While immunocheckpoint blockade has shown promising results, only 20-40 % of patients experience objective clinical benefit. Differences in individual tumor biology and the presence multiple immune checkpoints present a challenge for treatment...
September 23, 2016: Journal of Hematology & Oncology
T Mok, Y-L Wu, S Sadowski, J Zhang, R Rangwala, D Kush, G de Lima Lopes
No abstract text is available yet for this article.
April 2016: Journal of Thoracic Oncology
Toshio Shimizu, Takashi Seto, Fumihiko Hirai, Mitsuhiro Takenoyama, Kaname Nosaki, Junji Tsurutani, Hiroyasu Kaneda, Tsutomu Iwasa, Hisato Kawakami, Kazuo Noguchi, Takashi Shimamoto, Kazuhiko Nakagawa
Background This phase I study evaluated the safety and tolerability, pharmacokinetics and pharmacodynamics, immunogenicity, and antitumor activity of pembrolizumab in Japanese patients with advanced solid tumors. Methods Following an initial dose and a 28-day rest (cycle 1), pembrolizumab was administered as an intravenous infusion at escalating doses (2 or 10 mg/kg) every 2 weeks (Q2W) until disease progression or unacceptable toxicity. Adverse events (AEs) were assessed using CTCAE v4.0, and tumor response was assessed using both RECIST v1...
June 2016: Investigational New Drugs
Lajos Pusztai, Andrea Ladányi, Borbála Székely, Magdolna Dank
The prognostic value of tumor infiltrating lymphocytes in breast cancer has long been recognized by histopathologists. These observations were reaffirmed by recent immunohistochemistry and gene expression profiling studies that also revealed an association between greater chemotherapy sensitivity and extensive lymphocytic infiltration in early stage breast cancers treated with neoadjuvant chemotherapy. These results suggest that local anti-tumor immune response can at least partially control cancer growth and may mediate the antitumor effects of chemotherapy...
March 2, 2016: Magyar Onkologia
Safiya Karim, Natasha Leighl
New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit...
January 2016: Future Oncology
M Tan, L Quintal
WHAT IS KNOWN AND OBJECTIVE: To review the pharmacology, efficacy, safety, formulary and economic considerations of pembrolizumab, a novel, first-in-class, anti-PD-1 monoclonal antibody for treatment of advanced melanoma. METHODS: A literature search was conducted using PubMed (July 2013-December 2014) with search terms: pembrolizumab, MK-3475 and lambrolizumab. Additional sources were identified through a subsequent review of all relevant papers, clinicaltrials...
June 29, 2015: Journal of Clinical Pharmacy and Therapeutics
Meagan S Barbee, Adebayo Ogunniyi, Troy Z Horvat, Thu-Oanh Dang
OBJECTIVE: To provide the clinician with an update and the current status and future direction of approved immune checkpoint inhibitors (ICIs) in oncology. DATA SOURCES: A PubMed search from January 1, 1966 to March 13, 2015 was performed using the key terms ipilimumab, pembrolizumab, lambrolizumab, nivolumab, immune checkpoint inhibitor, MDX-010, MDX-101, BMS-734016, MK-3475, SCH 900475, MDX-1106, BMS-936558, ONO-4538, CTLA-4, PD-1, or PD-L1 and cancer, oncology, or neoplasm...
August 2015: Annals of Pharmacotherapy
Amita Patnaik, S Peter Kang, Drew Rasco, Kyriakos P Papadopoulos, Jeroen Elassaiss-Schaap, Muralidhar Beeram, Ronald Drengler, Cong Chen, Lon Smith, Guillermo Espino, Kevin Gergich, Liliana Delgado, Adil Daud, Jill A Lindia, Xiaoyun Nicole Li, Robert H Pierce, Jennifer H Yearley, Dianna Wu, Omar Laterza, Manfred Lehnert, Robert Iannone, Anthony W Tolcher
PURPOSE: This phase I study evaluated the safety, maximum tolerated dose, antitumor activity, and pharmacokinetics and pharmacodynamics of pembrolizumab in patients with advanced solid tumors. EXPERIMENTAL DESIGN: In a 3 + 3 dose escalation study, 10 patients received pembrolizumab 1, 3, or 10 mg/kg intravenously every 2 weeks until progression or intolerable toxicity. Seven additional patients received 10 mg/kg every 2 weeks. Thirteen patients participated in a 3-week intrapatient dose escalation (dose range, 0...
October 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Katelyn T Byrne, Robert H Vonderheide, Elizabeth M Jaffee, Todd D Armstrong
The overall objective of the fifth American Association for Cancer Research Special Conference, "Tumor Immunology and Immunotherapy: A New Chapter," organized by the Cancer Immunology Working Group, was to highlight multidisciplinary approaches of immunotherapy and mechanisms related to the ability of immunotherapy to fight established tumors. With the FDA approval of sipuleucel-T, ipilimumab (anti-CTLA-4; Bristol-Myers Squibb), and the two anti-PD-1 antibodies, pembrolizumab (formerly MK-3475 or lambrolizumab; Merck) and nivolumab (Bristol-Myers Squibb), immunotherapy has become a mainstream treatment option for some cancers...
May 12, 2015: Cancer Immunology Research
Blanca Homet Moreno, Giulia Parisi, Lidia Robert, Antoni Ribas
Immune-regulatory mechanisms are used by cancer to hide from the immune system. Advances and in-depth understanding of the biology of melanoma and its interaction with the immune system have led to the development of some of antagonistic antibodies to the programmed death 1 pathway (PD-1) and one of its ligands, programmed death ligand 1 (PD-L1), which are demonstrating high clinical benefit rates and tolerability. Blocking the immune-regulatory checkpoints that limit T-cell responses to melanoma upon PD-1/PD-L1 modulation has provided clinically validated targets for cancer immunotherapy...
June 2015: Seminars in Oncology
Tara C Gangadhar, April Ks Salama
Preclinical work has led to an increased understanding of the immunomodulatory mechanisms involved in the regulation of the antitumor response in a variety of tumor types. PD-1 (programmed death 1) appears to be a key checkpoint involved in immune suppression in the tumor microenvironment, even in diseases not previously thought to be sensitive to immune manipulation. More recently, the subsequent clinical development of PD-1-based therapy has resulted in a major breakthrough in the field of oncology. Pembrolizumab, a humanized highly selective IgG4 anti-PD-1 monoclonal antibody, was recently approved for the treatment of advanced melanoma based on promising early-phase clinical data...
2015: OncoTargets and Therapy
J McDermott, A Jimeno
Programmed cell death protein 1 (PD-1) and its ligands, programmed cell death 1 ligand 1 (PD-L1) and 2 (PD-L2) play an important role in regulating immune response through various mechanisms. This inhibitory action is thought to assist in immune evasion by cancer cells as PD-1, PD-L1 and PD-L2 have been found to be abnormally expressed by tumor cells and lymphocytes in the tumor microenvironment. Preclinical studies described PD-1 blockade resulting in tumor growth suppression and even decreased metastasis...
January 2015: Drugs of Today
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