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Presenters: Chad A. LaGrange, M. Dror Michaelson, and Colleen H. Tetzlaff

monotherapy, combination therapy with CTLA4/PD-1, or combination therapy with VEGFR TKI/PD-1. Two recent phase III trials of frontline treatment of RCC provide some guidance for treatment selection. 3 , 4 CheckMate 214 compared ipilimumab/nivolumab versus

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Tanya E. Keenan and Sara M. Tolaney

lymphocyte antigen-4 (CTLA-4) and PD-1, to improve the cytotoxicity and proliferative capacity of tumor-infiltrating lymphocytes (TILs). ICIs, including monoclonal antibodies against PD-1 (ie, pembrolizumab, nivolumab), PD-L1 (ie, atezolizumab, durvalumab

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Atish D. Choudhury and Philip W. Kantoff

to sipuleucel-T if also efficacious. Ipilimumab, a fully human monoclonal antibody targeting CTLA-4, a surface molecule that transduces inhibitory signals in T cells, is now being investigated in 2 randomized placebo-controlled phase III trials for

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NCCN Guidelines Insights: Kidney Cancer, Version 2.2020

Featured Updates to the NCCN Guidelines

Robert J. Motzer, Eric Jonasch, M. Dror Michaelson, Lakshminarayanan Nandagopal, John L. Gore, Saby George, Ajjai Alva, Naomi Haas, Michael R. Harrison, Elizabeth R. Plimack, Jeffrey Sosman, Neeraj Agarwal, Sam Bhayani, Toni K. Choueiri, Brian A. Costello, Ithaar H. Derweesh, Thomas H. Gallagher, Steven L. Hancock, Christos Kyriakopoulos, Chad LaGrange, Elaine T. Lam, Clayton Lau, Bryan Lewis, Brandon Manley, Brittany McCreery, Andrew McDonald, Amir Mortazavi, Phillip M. Pierorazio, Lee Ponsky, Bruce G. Redman, Bradley Somer, Geoffrey Wile, Mary A. Dwyer, CGC, Lydia J. Hammond, and Griselda Zuccarino-Catania

-presenting cells, including immune cells and tumor cells). Ipilimumab is an antibody that selectively blocks the interaction between the negative regulator CTLA-4 (expressed early on activated T cells) and its ligands CD80/CD86 (expressed on antigen

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Yuefeng Wang, Xinhua Yu, Nan Zhao, Jiajing Wang, Chi Lin, Enrique W. Izaguirre, Michael Farmer, Gary Tian, Bradley Somer, Nilesh Dubal, David L. Schwartz, Matthew T. Ballo, and Noam A. VanderWalde

improve responses to anti-CTLA-4 treatment . Vaccine 2015 ; 33 : 7415 – 7422 . 32. Golden EB Chhabra A Chachoua A . Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with

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Pooja Ghatalia and Elizabeth R. Plimack

studying nivolumab alone and in combination with the CTLA-4 inhibitor ipilimumab. The study included 3 cohorts with varying doses: nivolumab, 3 mg/kg (NIVO3) (n=78); nivolumab, 3 mg/kg + ipilimumab, 1 mg/kg (NIVO3+IPI1) (N=104); and nivolumab, 1 mg

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Matthew Zibelman and Elizabeth R. Plimack

metastatic melanoma using the combination of nivolumab with the cytotoxic T-lymphocyte–associated protein 4 (CTLA-4)–specific mAb ipilimumab. This combination demonstrated improved efficacy over both single agents, but with a consequent increase in grade 3

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David S. Ettinger, Douglas E. Wood, Wallace Akerley, Lyudmila A. Bazhenova, Hossein Borghaei, David Ross Camidge, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Thomas J. Dilling, M. Chris Dobelbower, Ramaswamy Govindan, Mark Hennon, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Rudy P. Lackner, Michael Lanuti, Rogerio Lilenbaum, Jules Lin, Billy W. Loo Jr., Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, Neelesh Sharma, James Stevenson, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, and Miranda Hughes

pathway are in clinical trials, notably atezolizumab and durvalumab, which target PD-L1. 15 – 17 In addition, clinical trials are ongoing in which PD-1/PD-L1 antibodies are combined with CTLA-4 antibodies. Although benefit from immune checkpoint

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NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2021

Featured Updates to the NCCN Guidelines

Susan M. Swetter, John A. Thompson, Mark R. Albertini, Christopher A. Barker, Joel Baumgartner, Genevieve Boland, Bartosz Chmielowski, Dominick DiMaio, Alison Durham, Ryan C. Fields, Martin D. Fleming, Anjela Galan, Brian Gastman, Kenneth Grossmann, Samantha Guild, Ashley Holder, Douglas Johnson, Richard W. Joseph, Giorgos Karakousis, Kari Kendra, Julie R. Lange, Ryan Lanning, Kim Margolin, Anthony J. Olszanski, Patrick A. Ott, Merrick I. Ross, April K. Salama, Rohit Sharma, Joseph Skitzki, Jeffrey Sosman, Evan Wuthrick, Nicole R. McMillian, and Anita M. Engh

.org). Treatment of Unresectable Stage III or Distant Metastatic Disease (Stage IV): Updates to Systemic Therapy Options Anti–PD-1/Anti–CTLA-4 Combinations For several years, combination therapy with nivolumab/ipilimumab has been a recommended option for

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Benjamin Levy, Ashish Saxena, and Bryan J. Schneider

apoptotic and hedgehog pathways, respectively. The insulin-like growth factor 1 receptor (IGF-1R) pathway may be deregulated in SCLC, and studies with the monoclonal antibody cixutumumab (IGF-1R antagonist) are underway. 65 The anti-CTLA-4 antibody