Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma
Robert J. Motzer,Bernard Escudier,David F. McDermott,Saby George,Hans J. Hammers,Sandhya Srinivas,Scott S. Tykodi,Jeffrey A. Sosman,Giuseppe Procopio,Elizabeth R. Plimack,Daniel Castellano,Toni K. Choueiri,Howard Gurney,Frede Donskov,Petri Bono,John Wagstaff,Thomas Gauler,Takeshi Ueda,Yoshihiko Tomita,Fabio A.B. Schutz,Christian Kollmannsberger,James Larkin,Alain Ravaud,Jason S. Simon,Li-an Xu,Ian M. Waxman,Padmanee Sharma +26 more
TLDR
Overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus among patients with previously treated advanced renal-cell carcinoma.Abstract:
BackgroundNivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment. MethodsA total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily. The primary end point was overall survival. The secondary end points included the objective response rate and safety. ResultsThe median overall survival was 25.0 months (95% confidence interval [CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 23.1) with everolimus. The haz...read more
Citations
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Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1.
Stéphane Champiat,Stéphane Champiat,Laurent Dercle,Samy Ammari,Christophe Massard,Antoine Hollebecque,Sophie Postel-Vinay,Sophie Postel-Vinay,Nathalie Chaput,Alexander M.M. Eggermont,Aurélien Marabelle,Aurélien Marabelle,Jean-Charles Soria,Jean-Charles Soria,Charles Ferté,Charles Ferté +15 more
TL;DR: A novel aggressive pattern of hyperprogressive disease or HPD exists in a fraction of patients treated with anti-PD-1/PD-L1 monotherapy, and this observation raises some concerns about treating elderly patients (>65 years old), and suggests further study of this phenomenon.
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Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial
Kohei Shitara,Mustafa Ozguroglu,Yung-Jue Bang,Maria Di Bartolomeo,Mario Mandalà,Min-Hee Ryu,Lorenzo Fornaro,Tomasz Olesinski,Christian Caglevic,Hyun Cheol Chung,Kei Muro,Eray Goekkurt,Wasat Mansoor,Raymond S. McDermott,Einat Shacham-Shmueli,X. Chen,Carlos Alberto Mayo,S. Peter Kang,Atsushi Ohtsu,Charles S. Fuchs,Guillermo Lerzo,Juan Manuel O'Connor,Guillermo Mendez,James Lynam,Niall C. Tebbutt,Mark Wong,Andrew Strickland,Chris Karapetis,David Goldstein,Paul Vasey,Jean-Luc Van Laethem,Eric Van Cutsem,Scott R. Berry,Mark Vincent,Bettina Muller,Felipe Rey,Angela Zambrano,Joaquin Guerra,Merete Krogh,Lene Baeksgaard,Mette Karen Yilmaz,Anneli Elme,Andrus Magi,Paivi Auvinen,Tuomo Alanko,Markus Moehler,Volker Kunzmann,Thomas Seufferlein,Peter C. Thuss-Patience,Thomas Hoehler,Georg Martin Haag,Salah-Eddin Al-Batran,Hugo Castro,Karla Lopez,Mynor Aguilar Vasquez,Mario Sandoval,Ka On Lam,Sinead Cuffe,Cathy Kelly,Ravit Geva,Ayala Hubert,Alex Beny,Baruch Brenner,Aprile Giuseppe,Alfredo Falcone,Evaristo Maiello,Rodolfo Passalacqua,Vincenzo Montesarchio,Hiroki Hara,Keisho Chin,Tomohiro Nishina,Yoshito Komatsu,Nozumo Machida,Shuichi Hironaka,Taroh Satoh,Takao Tamura,Naotaoshi Sugimoto,Haruhiko Cho,Yashushi Omuro,Ken Kato,Masahiro Goto,Ichinosuke Hyodo,Kazuhiro Yoshida,Hideo Baba,Taito Esaki,Junji Furuse,Wan Zamaniah Wan Mohammed,Carlos Hernandez Hernandez,Juan Casas Garcia,Adriana Dominguez Andrade,Katriona Clarke,Geir Hjortland,Nils Glenjen,Tomasz Kubiatowski,Jassem Jacek,Marek Z. Wojtukiewicz,Sergey Alexandrovich Lazarev,Yuri Lancukhay,Sergey Afanasayev,Vladimir Moiseyenko,Vladimir Kostorov,Svetlana Protsenko,Vadim Shirinkin,Dina Sakaeva,Natalia Fadeeva,Wei Peng Yong,Chau Hsien Matthew Ng,Barbara Robertson,Bernardo Rapaport,Graham Cohen,Lydia Dreosti,Paul Ruff,Conrad Jacobs,Gregory Landers,Waldemar Szpak,Sang-Young Roh,Jeeyun Lee,Yeul Hong Kim,Hyun Cheol Chung,Maria Alsina Maqueda,Federico Longo Munoz,Andres Cervantes Aguilar,Enrique Aranda Aguilar,Pilar Garcia Alfonso,Fernando Rivera,Jaime Feliu Batle,Roberto Pazo Cid,Kun-Huei Yeh,Jen-Shi Chen,Yee Chao,Chia Jui Yen,Oguz Kara,Suayib Yalcin,Daniel Hochhauser,Ian Chau,Al B. Benson,Veena Shankaran,Walid Shaib,Philip A. Philip,Vivek Sharma,Robert J. Siegel,Weijing Sun,Zev A. Wainberg,Ben George,Andrea J. Bullock,Samuel Myrick,Josephine Faruol,Richard M. Siegel,Timothy V. Larson,Carlos Becerra,Suresh Ratnam,Donald A. Richards,Stephen L. Riche +152 more
TL;DR: Pembrolizumab did not significantly improve overall survival compared with paclitaxel as second-line therapy for advanced gastric or gastro-oesophageal junction cancer with PD-L1 CPS of 1 or higher and had a better safety profile than pac litaxel.
Journal ArticleDOI
Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations.
TL;DR: Predictive biomarkers, mechanisms of resistance, hyperprogressors, treatment duration and treatment beyond progression, immune-related toxicities, and clinical trial design are key concepts in need of further consideration to optimize the anticancer potential of this class of immunotherapy.
Journal ArticleDOI
Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma
David F. McDermott,Mahrukh Huseni,Michael B. Atkins,Robert J. Motzer,Brian I. Rini,Bernard Escudier,Lawrence Fong,Richard W. Joseph,Sumanta K. Pal,James A. Reeves,Mario Sznol,John D. Hainsworth,W. Kimryn Rathmell,Walter M. Stadler,Thomas E. Hutson,Martin Gore,Alain Ravaud,Sergio Bracarda,Cristina Suarez,Riccardo Danielli,Viktor Gruenwald,Toni K. Choueiri,Dorothee Nickles,Suchit Jhunjhunwala,Elisabeth Piault-Louis,Alpa Thobhani,Jiaheng Qiu,Daniel S. Chen,Priti S. Hegde,Christina Schiff,Gregg Fine,Thomas Powles +31 more
TL;DR: Molecular profiles suggest that prediction of outcomes with anti-VEGF and immunotherapy may be possible and offer mechanistic insights into how blocking VEGF may overcome resistance to immune checkpoint blockade.
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
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TL;DR: Tirosh et al. as discussed by the authors applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells.
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