First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer
David P Carbone, Martin Reck, Luis Paz-Ares, Benjamin Creelan, Leora Horn, Martin Steins, Enriqueta Felip, Michel M van den Heuvel, Tudor-Eliade Ciuleanu, Firas Badin, Neal Ready, T Jeroen N Hiltermann, Suresh Nair, Rosalyn Juergens, Solange Peters, Elisa Minenza, John M Wrangle, Delvys Rodriguez-Abreu, Hossein Borghaei, George R Blumenschein Jr, Liza C Villaruz, Libor Havel, Jana Krejci, Jesus Corral Jaime, Han Chang, William J Geese, Prabhu Bhagavatheeswaran, Allen C Chen, Mark A Socinski, CheckMate 026 Investigators, Lorena Lupinacci, Claudio Martin, Norma Pilnik, Martin Eduardo Richardet, Mirta Susana Varela, Jacqueline Adams, Michael Boyer, Thomas John, Melissa Moore, Kenneth O'Byrne, Josef Eckmayr, Robert Pirker, Lore Decoster, Jan van Meerbeeck, Johan Vansteenkiste, Veerle Surmont, Carlos Henrique Barrios, Fabio Andre Franke, Gustavo Pinto, Normand Blais, Marie-Claude Foley, Rosalyn Juergens, Natasha Leighl, Don G Morris, Libor Havel, Vitezslav Kolek, Jana Krejci, Pavel Reiterer, Jaromir Roubec, Jarkko Ahvonen, Antti Jekunen, Paula Maasilta, Fabrice Barlesi, Eric Dansen, Gislaine Fraboulet, Herve Lena, Bertrand Mennecier, Gerard Zalcman, Norbert Frickhofen, Martin Kohlhaeufl, Martin Reck, Roland Repp, Martin Steins, Juergen Wolf, Sofia Agelaki, Konstantinos Syrigos, Istvan Albert, Gyula Ostoros, Maria Szilasi, Federico Cappuzzo, Lucio Crino, Filippo De Marinis, Cesare Gridelli, Alessandro Morabito, Fausto Roila, Shinji Atagi, Shiro Fujita, Toyoaki Hida, Tomonori Hirashima, Makoto Maemondo, Koichi Minato, Kazuhiko Nakagawa, Makoto Nishio, Naoyuki Nogami, Yuichiro Ohe, Hideo Saka, Hiroshi Sakai, Miyako Satouchi, Koji Takeda, Hiroshi Tanaka, Nobuyuki Yamamoto, Oscar Arrieta-Rodriguez, Emanuel De la Mora Jimenez, Victoria Flores Wilbert, Joachim Aerts, T Jeroen N Hiltermann, Michel Van Den Heuvel, Ewa Chmielowska, Grzegorz Czyzewicz, Jacek Gabrys, Ewa Kalinka-Warzocha, Adam Pluzanski, Hye Ryun Kim, Sang-We Kim, Keunchil Park, Calin Cainap, Tudor-Eliade Ciuleanu, Doru Ghizdavescu, Ana Blasco, Jesus Corral Jaime, Javier De Castro, Enriqueta Felip, Luis Paz-Ares, Delvys Rodriguez Abreu, Jose Trigo, Karl-Gustav Kölbeck, Magnus Lindskog, Alessandra Curioni-Fontecedro, Michael Mark, Solange Peters, Yuh-Min Chen, Halit Karaca, David Chao, Clive Mulatero, Yvonne Summers, Sherri Arledge, Firas Badin, Marta Batus, George Blumenschein, Hossein Borghaei, Ross Camidge, Thomas Boyd, Julie Brahmer, David Carbone, Jeremy Cetnar, Abraham Chachoua, Jamie Chaft, Hongbin Chen, Benjamin Creelan, Justin Gainor, Scott Gettinger, David E Gerber, Leora Horn, Paul Kaywin, Robert Kessler, Corey J Langer, Joseph McCracken, Suresh Nair, Raul Oyola, Rathi Pillai, Fahd Quddus, Deepa Rangachari, Neal Ready, Craig Reynolds, Richard Rosenberg, Neelesh Sharma, Thomas Stinchcombe, Liza Villaruz, Heather Wakelee, John Wrangle, David P Carbone, Martin Reck, Luis Paz-Ares, Benjamin Creelan, Leora Horn, Martin Steins, Enriqueta Felip, Michel M van den Heuvel, Tudor-Eliade Ciuleanu, Firas Badin, Neal Ready, T Jeroen N Hiltermann, Suresh Nair, Rosalyn Juergens, Solange Peters, Elisa Minenza, John M Wrangle, Delvys Rodriguez-Abreu, Hossein Borghaei, George R Blumenschein Jr, Liza C Villaruz, Libor Havel, Jana Krejci, Jesus Corral Jaime, Han Chang, William J Geese, Prabhu Bhagavatheeswaran, Allen C Chen, Mark A Socinski, CheckMate 026 Investigators, Lorena Lupinacci, Claudio Martin, Norma Pilnik, Martin Eduardo Richardet, Mirta Susana Varela, Jacqueline Adams, Michael Boyer, Thomas John, Melissa Moore, Kenneth O'Byrne, Josef Eckmayr, Robert Pirker, Lore Decoster, Jan van Meerbeeck, Johan Vansteenkiste, Veerle Surmont, Carlos Henrique Barrios, Fabio Andre Franke, Gustavo Pinto, Normand Blais, Marie-Claude Foley, Rosalyn Juergens, Natasha Leighl, Don G Morris, Libor Havel, Vitezslav Kolek, Jana Krejci, Pavel Reiterer, Jaromir Roubec, Jarkko Ahvonen, Antti Jekunen, Paula Maasilta, Fabrice Barlesi, Eric Dansen, Gislaine Fraboulet, Herve Lena, Bertrand Mennecier, Gerard Zalcman, Norbert Frickhofen, Martin Kohlhaeufl, Martin Reck, Roland Repp, Martin Steins, Juergen Wolf, Sofia Agelaki, Konstantinos Syrigos, Istvan Albert, Gyula Ostoros, Maria Szilasi, Federico Cappuzzo, Lucio Crino, Filippo De Marinis, Cesare Gridelli, Alessandro Morabito, Fausto Roila, Shinji Atagi, Shiro Fujita, Toyoaki Hida, Tomonori Hirashima, Makoto Maemondo, Koichi Minato, Kazuhiko Nakagawa, Makoto Nishio, Naoyuki Nogami, Yuichiro Ohe, Hideo Saka, Hiroshi Sakai, Miyako Satouchi, Koji Takeda, Hiroshi Tanaka, Nobuyuki Yamamoto, Oscar Arrieta-Rodriguez, Emanuel De la Mora Jimenez, Victoria Flores Wilbert, Joachim Aerts, T Jeroen N Hiltermann, Michel Van Den Heuvel, Ewa Chmielowska, Grzegorz Czyzewicz, Jacek Gabrys, Ewa Kalinka-Warzocha, Adam Pluzanski, Hye Ryun Kim, Sang-We Kim, Keunchil Park, Calin Cainap, Tudor-Eliade Ciuleanu, Doru Ghizdavescu, Ana Blasco, Jesus Corral Jaime, Javier De Castro, Enriqueta Felip, Luis Paz-Ares, Delvys Rodriguez Abreu, Jose Trigo, Karl-Gustav Kölbeck, Magnus Lindskog, Alessandra Curioni-Fontecedro, Michael Mark, Solange Peters, Yuh-Min Chen, Halit Karaca, David Chao, Clive Mulatero, Yvonne Summers, Sherri Arledge, Firas Badin, Marta Batus, George Blumenschein, Hossein Borghaei, Ross Camidge, Thomas Boyd, Julie Brahmer, David Carbone, Jeremy Cetnar, Abraham Chachoua, Jamie Chaft, Hongbin Chen, Benjamin Creelan, Justin Gainor, Scott Gettinger, David E Gerber, Leora Horn, Paul Kaywin, Robert Kessler, Corey J Langer, Joseph McCracken, Suresh Nair, Raul Oyola, Rathi Pillai, Fahd Quddus, Deepa Rangachari, Neal Ready, Craig Reynolds, Richard Rosenberg, Neelesh Sharma, Thomas Stinchcombe, Liza Villaruz, Heather Wakelee, John Wrangle
Abstract
Background: Nivolumab 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.
Methods: We 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.
Results: Among the 423 patients with a PD-L1 expression level of 5% or more, the median progression-free survival was 4.2 months with nivolumab versus 5.9 months with chemotherapy (hazard ratio for disease progression or death, 1.15; 95% confidence interval [CI], 0.91 to 1.45; P=0.25), and the median overall survival was 14.4 months versus 13.2 months (hazard ratio for death, 1.02; 95% CI, 0.80 to 1.30). A total of 128 of 212 patients (60%) in the chemotherapy group received nivolumab as subsequent therapy. Treatment-related adverse events of any grade occurred in 71% of the patients who received nivolumab and in 92% of those who received chemotherapy. Treatment-related adverse events of grade 3 or 4 occurred in 18% of the patients who received nivolumab and in 51% of those who received chemotherapy.
Conclusions: 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. Overall survival was similar between groups. Nivolumab had a favorable safety profile, as compared with chemotherapy, with no new or unexpected safety signals. (Funded by Bristol-Myers Squibb and others; CheckMate 026 ClinicalTrials.gov number, NCT02041533 .).
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Source: PubMed