First-Line Nivolumab in Stage IV or Recurrent Non–Small-Cell Lung Cancer
David P. Carbone,Martin Reck,Luis Paz-Ares,Benjamin C. Creelan,Leora Horn,Martin Steins,Enriqueta Felip,Michel M. van den Heuvel,Tudor-Eliade Ciuleanu,Firas Benyamine Badin,Neal Ready,T. Jeroen N. Hiltermann,Suresh G. Nair Md,Rosalyn A. Juergens,Solange Peters,Elisa Minenza,John Wrangle,Delvys Rodriguez-Abreu,Hossein Borghaei,George R. Blumenschein,Liza C. Villaruz,Libor Havel,Jana Krejci,Jesus Corral Jaime,Han Chang,William J. Geese,Prabhu Bhagavatheeswaran,Allen C. Chen,Mark A. Socinski +28 more
TLDR
Nivolumab was not associated with significantly longer progression‐free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD‐L1 expression level of 5% or more.Abstract:
BackgroundNivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non–small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)–positive NSCLC. MethodsWe randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more. ResultsAmong the 423 patients with a PD-L1 expression level of 5% or more, the media...read more
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Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer
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Bertrand Routy,Bertrand Routy,Bertrand Routy,Lisa Derosa,Lisa Derosa,Lisa Derosa,Connie P.M. Duong,Connie P.M. Duong,Maryam Tidjani Alou,Maryam Tidjani Alou,Maryam Tidjani Alou,Romain Daillère,Romain Daillère,Romain Daillère,Aurélie Fluckiger,Aurélie Fluckiger,Meriem Messaoudene,Meriem Messaoudene,Conrad Rauber,Conrad Rauber,Conrad Rauber,Maria Paula Roberti,Maria Paula Roberti,Marine Fidelle,Marine Fidelle,Caroline Flament,Caroline Flament,Vichnou Poirier-Colame,Vichnou Poirier-Colame,Paule Opolon,Christophe Klein,Kristina Iribarren,Laura Mondragón,Nicolas Jacquelot,Nicolas Jacquelot,Nicolas Jacquelot,Bo Qu,Bo Qu,Bo Qu,Gladys Ferrere,Gladys Ferrere,Gladys Ferrere,Céline Clémenson,Céline Clémenson,Laura Mezquita,Jordi Remon Masip,C. Naltet,Solenn Brosseau,Coureche Kaderbhai,Corentin Richard,Hira Rizvi,Florence Levenez,Nathalie Galleron,Benoit Quinquis,Nicolas Pons,Bernhard Ryffel,Veronique Minard-Colin,Patrick Gonin,Jean-Charles Soria,Eric Deutsch,Eric Deutsch,Yohann Loriot,Yohann Loriot,François Ghiringhelli,Gérard Zalcman,François Goldwasser,B. Escudier,B. Escudier,Matthew D. Hellmann,Matthew D. Hellmann,Alexander M.M. Eggermont,Alexander M.M. Eggermont,Didier Raoult,Laurence Albiges,Laurence Albiges,Guido Kroemer,Laurence Zitvogel +76 more
TL;DR: It is found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition, and Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer.
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TL;DR: Continued research into new drugs and combination therapies is required to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.
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Robert M. Samstein,Chung-Han Lee,Chung-Han Lee,Alexander N. Shoushtari,Alexander N. Shoushtari,Matthew D. Hellmann,Matthew D. Hellmann,Ronglai Shen,Yelena Y. Janjigian,Yelena Y. Janjigian,David Barron,Ahmet Zehir,Emmet Jordan,Antonio Omuro,Thomas Kaley,Sviatoslav M. Kendall,Robert J. Motzer,Robert J. Motzer,A. Ari Hakimi,Martin H. Voss,Martin H. Voss,Paul Russo,Jonathan E. Rosenberg,Jonathan E. Rosenberg,Gopa Iyer,Gopa Iyer,Bernard H. Bochner,Dean F. Bajorin,Dean F. Bajorin,Hikmat Al-Ahmadie,Jamie E. Chaft,Jamie E. Chaft,Charles M. Rudin,Charles M. Rudin,Gregory J. Riely,Gregory J. Riely,Shrujal S. Baxi,Shrujal S. Baxi,Alan L. Ho,Alan L. Ho,Richard J. Wong,David G. Pfister,David G. Pfister,Jedd D. Wolchok,Jedd D. Wolchok,Christopher A. Barker,Philip H. Gutin,Cameron Brennan,Viviane Tabar,Ingo K. Mellinghoff,Lisa M. DeAngelis,Charlotte E. Ariyan,Nancy Y. Lee,William D. Tap,William D. Tap,Mrinal M. Gounder,Mrinal M. Gounder,Sandra P. D'Angelo,Sandra P. D'Angelo,Leonard B. Saltz,Leonard B. Saltz,Zsofia K. Stadler,Zsofia K. Stadler,Howard I. Scher,Howard I. Scher,José Baselga,José Baselga,Pedram Razavi,Pedram Razavi,Christopher A. Klebanoff,Christopher A. Klebanoff,Rona Yaeger,Rona Yaeger,Neil H. Segal,Neil H. Segal,Geoffrey Y. Ku,Geoffrey Y. Ku,Ronald P. DeMatteo,Marc Ladanyi,Naiyer A. Rizvi,Michael F. Berger,Nadeem Riaz,David B. Solit,Timothy A. Chan,Luc G. T. Morris +84 more
TL;DR: Analysis of advanced cancer patients treated with immune-checkpoint inhibitors shows that tumor mutational burden, as assessed by targeted next-generation sequencing, predicts survival after immunotherapy across multiple cancer types.
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TL;DR: Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level.
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Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
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TL;DR: Treatment efficacy was associated with a higher number of mutations in the tumors, and a tumor-specific T cell response paralleled tumor regression in one patient, suggesting that the genomic landscape of lung cancers shapes response to anti–PD-1 therapy.
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