1. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer
- Author
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Heather, W, Moishe, L, Terufumi, K, Masahiro, T, Se-Hoon, L, Shugeng, G, Ke-Neng, C, Christophe, D, Margarita, M, Ekkehard, E, Gastón L, M, Olivier, B, Delvys, R, Jamie E, C, Silvia, N, Jing, Y, Steven M, K, Ayman, S, Spicer, D Marcelo Tatangelo, J, Flores, M, Pastor, A, Puig, J, Martinengo, G, Varela, M, Brocca, C, Wong, M, Hui, R, Dooms, C, Vansteenkiste, J, Demedts, I, Sibille, A, Surmont, V, Deschepper, K, Lambrechts, M, Dias, J, Rafael Martins De Marchi, P, Alves, G, Henrique Araujo, L, Matias, D, Chaves, F, Franke, F, Teixeira, C, Tabacof, J, Faria, L, Morbeck, I, Henrique Cronemberger, E, Lima, I, Sardenberg, R, de Paiva Junior, T, Dutra, C, Luiz Guimaraes, J, Begin, P, Langleben, A, Liu, G, Liberman, M, Spicer, J, Gao, S, Zhao, G, Jiang, T, Yan, X, Hu, J, Chen, J, Tan, L, Wang, Q, Li, S, Chen, K, Yang, Y, Bai, J, Ma, S, Chen, H, Chen, Q, Wang, W, Zhang, L, Zhu, Y, Vanakesa, T, Zasadny, X, Duchemann, B, Girard, N, Bylicki, O, Berard, H, Thiberville, L, Mennecier, B, Mazieres, J, Eigendorff, E, Bonnet, R, Fix, P, Reck, M, Rittmeyer, A, Reinacher-Schick, A, Wehler, T, Lehmann, M, Serke, M, Wesseler, C, Täuscher, D, Lang, S, Wermke, M, Grohe, C, Wirtz, H, Kollmeier, J, Ritgen, M, Mueller, A, Frohling, K, Vogel, G, Faehling, M, Cuffe, S, Collins, D, Delmonte, A, Gilli, M, Piantedosi, F, Ogliari, F, Bulotta, A, Gregorc, V, Gianni, L, Grisanti, S, Intagliata, S, Roca, E, Ferrari, V, Berruti, A, Cortinovis, D, Lo Russo, G, Ferrara, R, Garassino, M, Rita Migliorino, M, Novello, S, Santoro, A, Signorelli, D, Tsuboi, M, Okada, M, Kato, T, Nishio, W, Kuroda, H, Shimizu, J, Sakao, Y, Sugio, K, Horinouchi, H, Takamochi, K, Saji, H, Tanaka, F, Ikeda, N, Muto, S, Shio, Y, Suzuki, H, Hegmane, A, Cicenas, S, Zemaitis, M, Kek Pang, Y, Yew Heng, F, Leong Yu, K, Lowczak, A, Makles, K, Bryl, M, Zurawski, B, Pawlak, I, Han, J, Lee, S, Kim, J, Yong Shim, B, Cebotaru, C, Ganea, D, Scheusan, R, Ciurescu, I, Mazilu, L, Ungureanu, A, Gal, C, Ciubotaru, E, Iordan, I, Berceanu-Ion, R, Ciuleanu, T, Laktionov, K, Karaseva, N, Smagina, M, Luft, A, Afanasyev, S, Nesterova, A, Levchenko, E, Arkhipov, A, Fedenko, A, Ruff, P, Jacobs, C, Fourie, S, Carcereny, E, Calles Blanco, A, Rodriguez Abreu, D, Majem Tarruella, M, Bosch Barrera, J, Bernabe Caro, R, Nadal Alforja, E, Martnez Marti, A, Liao, B, Huang, H, Chiu, C, Wang, C, Tsai, C, Voitko, N, Kryzhanivska, A, Kolesnik, O, Levenko, O, Bondarenko, I, Trukhin, D, Ursol, G, Paramonov, V, Sokur, I, Khan, S, Arora, A, Goranov, B, Greystoke, A, Ahmed, S, Pope, T, O'Brien, M, Charu, V, Cobb, P, Costin, D, Weksler, B, Schumacher, L, Finley, G, Furqan, M, Gentzler, R, Misleh, J, Guarino, M, Halmos, B, Keresztes, R, Jain, K, Yan Lou, Y, Molina, J, Liu-Dumlao, T, Zhao, Q, Niu, J, Taysir Hammoud, Z, Rybkin, I, Cuevo, R, Fernando, H, Schiller, J, Srkalovic, G, Koontz, M, Stampleman, L, Anderson, I, Villaruz, L, Wang, S, Komiya, T, Jain, S, Starodub, A, Wakelee, H, Kishor Ganti, A, Ernani, V, Kristedja, T, O'Day, S, Radhi, S, Sangal, A, Duvivier, H, Rich, P, Kazmi, S, Pollock, T, Chaft, J, Rathnasabapathy, C, Savvides, P, Costas, K, Kaywin, P, Villalona-Calero, M, Alekshun, T, Rao, S, Siegel, R, Wakelee, Heather, Liberman, Moishe, Kato, Terufumi, Tsuboi, Masahiro, Lee, Se-Hoon, Gao, Shugeng, Chen, Ke-Neng, Dooms, Christophe, Majem, Margarita, Eigendorff, Ekkehard, Martinengo, Gastón L, Bylicki, Olivier, Rodríguez-Abreu, Delvys, Chaft, Jamie E, Novello, Silvia, Yang, Jing, Keller, Steven M, Samkari, Ayman, Jonathan D Marcelo Tatangelo, Marcos Flores, Andrea Pastor, Juan Puig, Gaston Martinengo, Mirta Varela, Carlos Brocca, Mark Wong, Rina Hui, Christophe Dooms, Johan Vansteenkiste, Ingel Demedts, Anne Sibille, Veerle Surmont, Koenraad Deschepper, Marc Lambrechts, Josiane Dias, Pedro Rafael Martins De Marchi, Gustavo Alves, Luiz Henrique Araujo, Danielli Matias, Fabio Chaves, Fabio Franke, Carlos Teixeira, Jacques Tabacof, Luiza Faria, Igor Morbeck, Eduardo Henrique Cronemberger, Iane Lima, Rodrigo Sardenberg, Tadeu de Paiva Junior, Carolina Dutra, Jose Luiz Guimaraes, Paul Begin, Adrian Langleben, Geoffrey Liu, Moishe Liberman, Jonathan Spicer, Shugeng Gao, Guofang Zhao, Tao Jiang, Xiaolong Yan, Jian Hu, Jun Chen, Lijie Tan, Qun Wang, Shanqing Li, Keneng Chen, Yue Yang, Jie Bai, Shaohua Ma, Haiquan Chen, Qixun Chen, Wenxiang Wang, Lanjun Zhang, Yuming Zhu, Tonu Vanakesa, Xavier Zasadny, Boris Duchemann, Nicolas Girard, Olivier Bylicki, Henri Berard, Luc Thiberville, Bertrand Mennecier, Julien Mazieres, Ekkehard Eigendorff, Reiner Bonnet, Peter Fix, Martin Reck, Achim Rittmeyer, Anke Reinacher-Schick, Thomas Wehler, Markus Lehmann, Monika Serke, Claas Wesseler, Dagmar Täuscher, Susanne Lang, Martin Wermke, Christian Grohe, Hubert Wirtz, Jens Kollmeier, Mathias Ritgen, Annette Mueller, Klaus-Peter Frohling, Gunther Vogel, Martin Faehling, Sinead Cuffe, Dearbhaile Collins, Angelo Delmonte, Marina Gilli, Francovito Piantedosi, Francesca Ogliari, Alessandra Bulotta, Vanesa Gregorc, Luca Gianni, Salvatore Grisanti, Salvatore Intagliata, Elisa Roca, Vittorio Ferrari, Alfredo Berruti, Diego Cortinovis, Giuseppe Lo Russo, Roberto Ferrara, Marina Garassino, Maria Rita Migliorino, Silvia Novello, Armando Santoro, Diego Signorelli, Masahiro Tsuboi, Morihito Okada, Terufumi Kato, Wataru Nishio, Hiroaki Kuroda, Junichi Shimizu, Yukinori Sakao, Kenji Sugio, Hidehito Horinouchi, Kazuya Takamochi, Hisashi Saji, Fumihiro Tanaka, Norihiko Ikeda, Satoshi Muto, Yutaka Shio, Hiroyuki Suzuki, Alinta Hegmane, Saulius Cicenas, Marius Zemaitis, Yong Kek Pang, Fook Yew Heng, Kong Leong Yu, Anna Lowczak, Krytsyna Makles, Maciej Bryl, Bogdan Zurawski, Ireneusz Pawlak, Ji-Youn Han, Se-Hoon Lee, Jhingook Kim, Byoung Yong Shim, Cristina Cebotaru, Doina Ganea, Roxana Scheusan, Ioana Ciurescu, Laura Mazilu, Andrei Ungureanu, Cristian Gal, Elena Ciubotaru, Ingrid Iordan, Radu Berceanu-Ion, Tudor Ciuleanu, Konstantin Laktionov, Nina Karaseva, Maria Smagina, Alexander Luft, Sergey Afanasyev, Alfiya Nesterova, Evgeny Levchenko, Alexander Arkhipov, Alexander Fedenko, Paul Ruff, Conrad Jacobs, Samuel Fourie, Enric Carcereny, Antonio Calles Blanco, Delvys Rodriguez Abreu, Margarita Majem Tarruella, Joaquim Bosch Barrera, Reyes Bernabe Caro, Ernest Nadal Alforja, Alex Martnez Marti, Bin-Chi Liao, Hsu-Ching Huang, Chao-Hua Chiu, Chin-Chou Wang, Chen-Liang Tsai, Nataliia Voitko, Anna Kryzhanivska, Olena Kolesnik, Oleh Levenko, Oleksii Kolesnik, Igor Bondarenko, Dmytro Trukhin, Grygorii Ursol, Viktor Paramonov, Iryna Sokur, Sarah Khan, Arvind Arora, Bojidar Goranov, Alastair Greystoke, Samreen Ahmed, Tony Pope, Mary O'Brien, Veena Charu, Patrick Cobb, Dan Costin, Benny Weksler, Lana Schumacher, Gene Finley, Muhammad Furqan, Ryan Gentzler, Jamal Misleh, Michael Guarino, Balazs Halmos, Roger Keresztes, Kirti Jain, Yan Yan Lou, Julian Molina, Theresa Liu-Dumlao, Qing Zhao, Jiaxin Niu, Zane Taysir Hammoud, Igor Rybkin, Raymund Cuevo, Hiran Fernando, Joan Schiller, Gordan Srkalovic, Michael Koontz, Laura Stampleman, Ian Anderson, Liza Villaruz, Sarah Wang, Takefumi Komiya, Sushil Jain, Alexander Starodub, Heather Wakelee, Apar Kishor Ganti, Vinicius Ernani, Timothy Kristedja, Steven O'Day, Saba Radhi, Ashish Sangal, Herbert Duvivier, Patricia Rich, Shayma Kazmi, Theodore Pollock, Jamie Chaft, Chenthilmurugan Rathnasabapathy, Panayiotis Savvides, Kimberly Costas, Paul Kaywin, Miguel Villalona-Calero, Todd Alekshun, Kevin Chen, Suman Rao, Robert Siegel, Heather, W, Moishe, L, Terufumi, K, Masahiro, T, Se-Hoon, L, Shugeng, G, Ke-Neng, C, Christophe, D, Margarita, M, Ekkehard, E, Gastón L, M, Olivier, B, Delvys, R, Jamie E, C, Silvia, N, Jing, Y, Steven M, K, Ayman, S, Spicer, D Marcelo Tatangelo, J, Flores, M, Pastor, A, Puig, J, Martinengo, G, Varela, M, Brocca, C, Wong, M, Hui, R, Dooms, C, Vansteenkiste, J, Demedts, I, Sibille, A, Surmont, V, Deschepper, K, Lambrechts, M, Dias, J, Rafael Martins De Marchi, P, Alves, G, Henrique Araujo, L, Matias, D, Chaves, F, Franke, F, Teixeira, C, Tabacof, J, Faria, L, Morbeck, I, Henrique Cronemberger, E, Lima, I, Sardenberg, R, de Paiva Junior, T, Dutra, C, Luiz Guimaraes, J, Begin, P, Langleben, A, Liu, G, Liberman, M, Spicer, J, Gao, S, Zhao, G, Jiang, T, Yan, X, Hu, J, Chen, J, Tan, L, Wang, Q, Li, S, Chen, K, Yang, Y, Bai, J, Ma, S, Chen, H, Chen, Q, Wang, W, Zhang, L, Zhu, Y, Vanakesa, T, Zasadny, X, Duchemann, B, Girard, N, Bylicki, O, Berard, H, Thiberville, L, Mennecier, B, Mazieres, J, Eigendorff, E, Bonnet, R, Fix, P, Reck, M, Rittmeyer, A, Reinacher-Schick, A, Wehler, T, Lehmann, M, Serke, M, Wesseler, C, Täuscher, D, Lang, S, Wermke, M, Grohe, C, Wirtz, H, Kollmeier, J, Ritgen, M, Mueller, A, Frohling, K, Vogel, G, Faehling, M, Cuffe, S, Collins, D, Delmonte, A, Gilli, M, Piantedosi, F, Ogliari, F, Bulotta, A, Gregorc, V, Gianni, L, Grisanti, S, Intagliata, S, Roca, E, Ferrari, V, Berruti, A, Cortinovis, D, Lo Russo, G, Ferrara, R, Garassino, M, Rita Migliorino, M, Novello, S, Santoro, A, Signorelli, D, Tsuboi, M, Okada, M, Kato, T, Nishio, W, Kuroda, H, Shimizu, J, Sakao, Y, Sugio, K, Horinouchi, H, Takamochi, K, Saji, H, Tanaka, F, Ikeda, N, Muto, S, Shio, Y, Suzuki, H, Hegmane, A, Cicenas, S, Zemaitis, M, Kek Pang, Y, Yew Heng, F, Leong Yu, K, Lowczak, A, Makles, K, Bryl, M, Zurawski, B, Pawlak, I, Han, J, Lee, S, Kim, J, Yong Shim, B, Cebotaru, C, Ganea, D, Scheusan, R, Ciurescu, I, Mazilu, L, Ungureanu, A, Gal, C, Ciubotaru, E, Iordan, I, Berceanu-Ion, R, Ciuleanu, T, Laktionov, K, Karaseva, N, Smagina, M, Luft, A, Afanasyev, S, Nesterova, A, Levchenko, E, Arkhipov, A, Fedenko, A, Ruff, P, Jacobs, C, Fourie, S, Carcereny, E, Calles Blanco, A, Rodriguez Abreu, D, Majem Tarruella, M, Bosch Barrera, J, Bernabe Caro, R, Nadal Alforja, E, Martnez Marti, A, Liao, B, Huang, H, Chiu, C, Wang, C, Tsai, C, Voitko, N, Kryzhanivska, A, Kolesnik, O, Levenko, O, Bondarenko, I, Trukhin, D, Ursol, G, Paramonov, V, Sokur, I, Khan, S, Arora, A, Goranov, B, Greystoke, A, Ahmed, S, Pope, T, O'Brien, M, Charu, V, Cobb, P, Costin, D, Weksler, B, Schumacher, L, Finley, G, Furqan, M, Gentzler, R, Misleh, J, Guarino, M, Halmos, B, Keresztes, R, Jain, K, Yan Lou, Y, Molina, J, Liu-Dumlao, T, Zhao, Q, Niu, J, Taysir Hammoud, Z, Rybkin, I, Cuevo, R, Fernando, H, Schiller, J, Srkalovic, G, Koontz, M, Stampleman, L, Anderson, I, Villaruz, L, Wang, S, Komiya, T, Jain, S, Starodub, A, Wakelee, H, Kishor Ganti, A, Ernani, V, Kristedja, T, O'Day, S, Radhi, S, Sangal, A, Duvivier, H, Rich, P, Kazmi, S, Pollock, T, Chaft, J, Rathnasabapathy, C, Savvides, P, Costas, K, Kaywin, P, Villalona-Calero, M, Alekshun, T, Rao, S, Siegel, R, Wakelee, Heather, Liberman, Moishe, Kato, Terufumi, Tsuboi, Masahiro, Lee, Se-Hoon, Gao, Shugeng, Chen, Ke-Neng, Dooms, Christophe, Majem, Margarita, Eigendorff, Ekkehard, Martinengo, Gastón L, Bylicki, Olivier, Rodríguez-Abreu, Delvys, Chaft, Jamie E, Novello, Silvia, Yang, Jing, Keller, Steven M, Samkari, Ayman, Jonathan D Marcelo Tatangelo, Marcos Flores, Andrea Pastor, Juan Puig, Gaston Martinengo, Mirta Varela, Carlos Brocca, Mark Wong, Rina Hui, Christophe Dooms, Johan Vansteenkiste, Ingel Demedts, Anne Sibille, Veerle Surmont, Koenraad Deschepper, Marc Lambrechts, Josiane Dias, Pedro Rafael Martins De Marchi, Gustavo Alves, Luiz Henrique Araujo, Danielli Matias, Fabio Chaves, Fabio Franke, Carlos Teixeira, Jacques Tabacof, Luiza Faria, Igor Morbeck, Eduardo Henrique Cronemberger, Iane Lima, Rodrigo Sardenberg, Tadeu de Paiva Junior, Carolina Dutra, Jose Luiz Guimaraes, Paul Begin, Adrian Langleben, Geoffrey Liu, Moishe Liberman, Jonathan Spicer, Shugeng Gao, Guofang Zhao, Tao Jiang, Xiaolong Yan, Jian Hu, Jun Chen, Lijie Tan, Qun Wang, Shanqing Li, Keneng Chen, Yue Yang, Jie Bai, Shaohua Ma, Haiquan Chen, Qixun Chen, Wenxiang Wang, Lanjun Zhang, Yuming Zhu, Tonu Vanakesa, Xavier Zasadny, Boris Duchemann, Nicolas Girard, Olivier Bylicki, Henri Berard, Luc Thiberville, Bertrand Mennecier, Julien Mazieres, Ekkehard Eigendorff, Reiner Bonnet, Peter Fix, Martin Reck, Achim Rittmeyer, Anke Reinacher-Schick, Thomas Wehler, Markus Lehmann, Monika Serke, Claas Wesseler, Dagmar Täuscher, Susanne Lang, Martin Wermke, Christian Grohe, Hubert Wirtz, Jens Kollmeier, Mathias Ritgen, Annette Mueller, Klaus-Peter Frohling, Gunther Vogel, Martin Faehling, Sinead Cuffe, Dearbhaile Collins, Angelo Delmonte, Marina Gilli, Francovito Piantedosi, Francesca Ogliari, Alessandra Bulotta, Vanesa Gregorc, Luca Gianni, Salvatore Grisanti, Salvatore Intagliata, Elisa Roca, Vittorio Ferrari, Alfredo Berruti, Diego Cortinovis, Giuseppe Lo Russo, Roberto Ferrara, Marina Garassino, Maria Rita Migliorino, Silvia Novello, Armando Santoro, Diego Signorelli, Masahiro Tsuboi, Morihito Okada, Terufumi Kato, Wataru Nishio, Hiroaki Kuroda, Junichi Shimizu, Yukinori Sakao, Kenji Sugio, Hidehito Horinouchi, Kazuya Takamochi, Hisashi Saji, Fumihiro Tanaka, Norihiko Ikeda, Satoshi Muto, Yutaka Shio, Hiroyuki Suzuki, Alinta Hegmane, Saulius Cicenas, Marius Zemaitis, Yong Kek Pang, Fook Yew Heng, Kong Leong Yu, Anna Lowczak, Krytsyna Makles, Maciej Bryl, Bogdan Zurawski, Ireneusz Pawlak, Ji-Youn Han, Se-Hoon Lee, Jhingook Kim, Byoung Yong Shim, Cristina Cebotaru, Doina Ganea, Roxana Scheusan, Ioana Ciurescu, Laura Mazilu, Andrei Ungureanu, Cristian Gal, Elena Ciubotaru, Ingrid Iordan, Radu Berceanu-Ion, Tudor Ciuleanu, Konstantin Laktionov, Nina Karaseva, Maria Smagina, Alexander Luft, Sergey Afanasyev, Alfiya Nesterova, Evgeny Levchenko, Alexander Arkhipov, Alexander Fedenko, Paul Ruff, Conrad Jacobs, Samuel Fourie, Enric Carcereny, Antonio Calles Blanco, Delvys Rodriguez Abreu, Margarita Majem Tarruella, Joaquim Bosch Barrera, Reyes Bernabe Caro, Ernest Nadal Alforja, Alex Martnez Marti, Bin-Chi Liao, Hsu-Ching Huang, Chao-Hua Chiu, Chin-Chou Wang, Chen-Liang Tsai, Nataliia Voitko, Anna Kryzhanivska, Olena Kolesnik, Oleh Levenko, Oleksii Kolesnik, Igor Bondarenko, Dmytro Trukhin, Grygorii Ursol, Viktor Paramonov, Iryna Sokur, Sarah Khan, Arvind Arora, Bojidar Goranov, Alastair Greystoke, Samreen Ahmed, Tony Pope, Mary O'Brien, Veena Charu, Patrick Cobb, Dan Costin, Benny Weksler, Lana Schumacher, Gene Finley, Muhammad Furqan, Ryan Gentzler, Jamal Misleh, Michael Guarino, Balazs Halmos, Roger Keresztes, Kirti Jain, Yan Yan Lou, Julian Molina, Theresa Liu-Dumlao, Qing Zhao, Jiaxin Niu, Zane Taysir Hammoud, Igor Rybkin, Raymund Cuevo, Hiran Fernando, Joan Schiller, Gordan Srkalovic, Michael Koontz, Laura Stampleman, Ian Anderson, Liza Villaruz, Sarah Wang, Takefumi Komiya, Sushil Jain, Alexander Starodub, Heather Wakelee, Apar Kishor Ganti, Vinicius Ernani, Timothy Kristedja, Steven O'Day, Saba Radhi, Ashish Sangal, Herbert Duvivier, Patricia Rich, Shayma Kazmi, Theodore Pollock, Jamie Chaft, Chenthilmurugan Rathnasabapathy, Panayiotis Savvides, Kimberly Costas, Paul Kaywin, Miguel Villalona-Calero, Todd Alekshun, Kevin Chen, Suman Rao, and Robert Siegel
- Abstract
BACKGROUND Among patients with resectable early-stage non-small-cell lung cancer (NSCLC), a perioperative approach that includes both neoadjuvant and adjuvant immune checkpoint inhibition may provide benefit beyond either approach alone. METHODS We conducted a randomized, double-blind, phase 3 trial to evaluate perioperative pembrolizumab in patients with early-stage NSCLC. Participants with resectable stage II, IIIA, or IIIB (N2 stage) NSCLC were assigned in a 1:1 ratio to receive neoadjuvant pembrolizumab (200 mg) or placebo once every 3 weeks, each of which was given with cisplatin-based chemotherapy for 4 cycles, followed by surgery and adjuvant pembrolizumab (200 mg) or placebo once every 3 weeks for up to 13 cycles. The dual primary end points were event-free survival (the time from randomization to the first occurrence of local progression that precluded the planned surgery, unresectable tumor, progression or recurrence, or death) and overall survival. Secondary end points included major pathological response, pathological complete response, and safety. RESULTS A total of 397 participants were assigned to the pembrolizumab group, and 400 to the placebo group. At the prespecified first interim analysis, the median follow-up was 25.2 months. Event-free survival at 24 months was 62.4% in the pembrolizumab group and 40.6% in the placebo group (hazard ratio for progression, recurrence, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.72; P<0.001). The estimated 24-month overall survival was 80.9% in the pembrolizumab group and 77.6% in the placebo group (P = 0.02, which did not meet the significance criterion). A major pathological response occurred in 30.2% of the participants in the pembrolizumab group and in 11.0% of those in the placebo group (difference, 19.2 percentage points; 95% CI, 13.9 to 24.7; P<0.0001; threshold, P = 0.0001), and a pathological complete response occurred in 18.1% and 4.0%, respectively (difference, 14.2 percentage points
- Published
- 2023