Search

Your search keyword '"Cuffe, S."' showing total 355 results
Start Over Author "Cuffe, S."
355 results on '"Cuffe, S."'

4. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer

Author

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

7. 32P Impact of smoking status on the relative efficacy of the EGFR TKI/angiogenesis inhibitor combination therapy in advanced NSCLC: A systematic review and meta-analysis

Author

Dafni, U., primary, Soo, R.A., additional, Peters, S., additional, Tsourti, Z., additional, Vervita, K., additional, Han, J-Y., additional, De Castro, J., additional, Coate, L., additional, Früh, M., additional, Hashemi, S.M.S., additional, Nadal, E., additional, Carcereny, E., additional, Angeles Sala González, M., additional, Bernabé Caro, R., additional, Provencio Pulla, M., additional, Cuffe, S., additional, Ruepp, B., additional, Roschitzki-Voser, H., additional, Rosell, R., additional, and Stahel, R.A., additional

Published
2022
Full Text
View/download PDF

8. A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial

Author

Sooy, R. A. Han, J. -Y. Dafni, U. Cho, B. C. Yeo, C. M. and Nadal, E. Carcereny, E. de Castro, J. Sala, M. A. and Bernabe, R. Coate, L. Provencio Pulla, M. Campelo, R. Garcia and Cuffe, S. Hashemi, S. M. S. Fruh, M. Massuti, B. and Garcia-Sanchez, J. Domine, M. Majem, M. Sanchez-Torres, J. -M. Britschgi, C. Pless, M. Dimopoulou, G. and Roschitzki-Voser, H. Ruepp, B. Rosell, R. Stahel, R. A. and Peters, S. ETOP 10-16 BOOSTER Collaborators

Abstract

Background: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. Patients and methods: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). Results: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8- 32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade >= 3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. Conclusions: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade >= 3 TRAEs were more common in patients on combination.

Published
2022

9. A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial

Author

Soo, R.A., primary, Han, J.-Y., additional, Dafni, U., additional, Cho, B.C., additional, Yeo, C.M., additional, Nadal, E., additional, Carcereny, E., additional, de Castro, J., additional, Sala, M.A., additional, Bernabé, R., additional, Coate, L., additional, Provencio Pulla, M., additional, Garcia Campelo, R., additional, Cuffe, S., additional, Hashemi, S.M.S., additional, Früh, M., additional, Massuti, B., additional, Garcia-Sanchez, J., additional, Dómine, M., additional, Majem, M., additional, Sanchez-Torres, J.-M., additional, Britschgi, C., additional, Pless, M., additional, Dimopoulou, G., additional, Roschitzki-Voser, H., additional, Ruepp, B., additional, Rosell, R., additional, Stahel, R.A., additional, Peters, S., additional, Stahel, Rolf, additional, Peters, Solange, additional, Soo, Ross, additional, Han, Ji-Youn, additional, Früh, Martin, additional, Provencio, Mariano, additional, Coate, Linda, additional, Dafni, Urania, additional, Hiltbrunner, Anita, additional, Ruepp, Barbara, additional, Roschitzki-Voser, Heidi, additional, Gasca-Ruchti, Adriana, additional, Giacomelli, Nino, additional, Kammler, Rosita, additional, Marti, Nesa, additional, Nobs, Lionel, additional, Pardo-Contreras, Mariana, additional, Pfister, Rita, additional, Piguet, Anne-Christine, additional, Ribeli-Hofmann, Sabrina, additional, Martinez, Virginia Rodriguez, additional, Roux, Susanne, additional, Sanchez-Hohl, Magdalena, additional, Schneider, Mirjam, additional, Schweri, Robin, additional, Troesch, Sandra, additional, Zigomo, Isabel, additional, Tsourti, Zoi, additional, Zygoura, Panagiota, additional, Kassapian, Marie, additional, Vervita, Katerina, additional, Dimopoulou, Georgia, additional, Andriakopoulou, Charitini, additional, Fernandez, Maria, additional, Pereira, Eva, additional, Simona, Carolina, additional, Tucker, Lisa, additional, Burnes, Jillian, additional, Barrett, Aisling, additional, McGrillen, Meghan, additional, Berset, Catherine, additional, Biaggi, Christine, additional, Reist, Martin, additional, Rentsch, Priska, additional, Cuffe, Sinead, additional, Hashemi, Sayed, additional, Nadal, Ernest, additional, Carcereny, Enric, additional, de Castro, Javier, additional, Sala, Maria Angeles, additional, Reyes, Bernabé, additional, Pulla, Mariano Provencio, additional, Campelo, Rosario Garcia, additional, Massutí, Bartomeu, additional, Garcia, Jose, additional, Dómine, Manuel, additional, Majem, Margarita, additional, Sanchez, Jose Miguel, additional, Britschgi, Christian, additional, Pless, Miklos, additional, Yeo, Chong Ming, additional, and Cho, Byoung Chul, additional

Published
2022
Full Text
View/download PDF

15. VP3-2021: A randomized phase II study of second-line osimertinib (Osi) and bevacizumab (Bev) versus Osi in advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) and T790M mutations (mt): Results from the ETOP BOOSTER trial

Author

Soo, R., Han, J-Y., Dimopoulou, G., Cho, B.C., Yeo, C.M., Nadal, E., Carcereny, E., de Castro, J., Sala, M.A., Bernabe, R., Coate, L., Provencio, M., Campelo, R. Garcia, Cuffe, S., Hashemi, S., Früh, M., Ruepp, B., Roschitzki-Voser, H., Stahel, R., and Peters, S.

Published
2021
Full Text
View/download PDF

17. Evolution and Clinical Impact of EGFR Mutations in Circulating Free DNA in the BELIEF Trial

Author

Molina-Vila, M.-A. Stahel, R.A. Dafni, U. Jordana-Ariza, N. Balada-Bel, A. Garzón-Ibáñez, M. García-Peláez, B. Mayo-de-las-Casas, C. Felip, E. Curioni Fontecedro, A. Gautschi, O. Peters, S. Massutí, B. Palmero, R. Ponce Aix, S. Carcereny, E. Früh, M. Pless, M. Popat, S. Cuffe, S. Bidoli, P. Kammler, R. Roschitzki-Voser, H. Tsourti, Z. Karachaliou, N. Rosell, R.

Abstract

Introduction: Longitudinal evaluation of mutations in blood samples was a prespecified secondary objective in the BELIEF trial of erlotinib and bevacizumab in advanced EGFR-positive NSCLC. Here, we report the testing results and explore the correlation of EGFR status in blood with clinical outcomes. Methods: Blood samples were prospectively collected from patients at baseline, at response evaluation, and at progression and sent to a central laboratory. Circulating free DNA was purified and EGFR mutations were analyzed with a validated real-time quantitative polymerase chain reaction assay. Results: EGFR exon 19/21 mutations were detected in 55 of 91 baseline blood samples (60.4%) and correlated with a significantly worse progression-free survival: 11.4 months (95% confidence interval [CI]: 9.0−14.8 mo) for the patients who were positive versus 22.9 months (95% CI: 9.5−33.9 mo) for those who were negative (log-rank p = 0.0020). Among the 74 samples at response, exon 19/21 mutations were detected only in three samples (4.1%). In contrast, 29 of 58 patients (50.0%) were exon 19/21 positive at progression and showed a significantly worse median overall survival of 21.7 months (95% CI: 17.0−30.9 mo) compared with 37.4 months (95% CI: 22.6−53.1 mo) for those who were negative (log-rank p = 0.011). Blood samples at the three time points were available for 48 patients. Of those, among 14 exon 19/21 EGFR-negative at presentation, 13 (93%) were persistently negative for the sensitizing mutations after progression and the p.T790M could only be detected in the blood of two patients. Conclusions: Longitudinal testing of EGFR mutations in blood can offer valuable clinical information. In patients of the BELIEF study, detection of EGFR mutations in circulating free DNA at presentation was associated with shorter progression-free survival, whereas positivity at progression correlated with shorter overall survival. Finally, patients negative in blood at presentation were almost invariably negative at relapse. © 2019

Published
2020

18. A Randomized Open-Label Phase III Trial Evaluating the Addition of Denosumab to Standard First-Line Treatment in Advanced NSCLC: The European Thoracic Oncology Platform (ETOP) and European Organisation for Research and Treatment of Cancer (EORTC) SPLENDOUR Trial

Author

Peters, S. Danson, S. Hasan, B. Dafni, U. Reinmuth, N. Majem, M. Tournoy, K.G. Mark, M.T. Pless, M. Cobo, M. Rodriguez-Abreu, D. Falchero, L. Moran, T. Ortega Granados, A.L. Monnet, I. Mohorcic, K. Sureda, B.M. Betticher, D. Demedts, I. Macias, J.A. Cuffe, S. Luciani, A. Sanchez, J.G. Curioni-Fontecedro, A. Gautschi, O. Price, G. Coate, L. von Moos, R. Zielinski, C. Provencio, M. Menis, J. Ruepp, B. Pochesci, A. Roschitzki-Voser, H. Besse, B. Rabaglio, M. O'Brien, M.E.R. Stahel, R.A.

Abstract

Introduction: Receptor activator of NF-kB ligand stimulates NF-kB–dependent cell signaling and acts as the primary signal for bone resorption. Retrospective analysis of a large trial comparing denosumab versus zoledronic acid in bone metastatic solid tumors suggested significant overall survival (OS) advantage for patients with lung cancer with denosumab (p = 0.01). The randomized open-label phase III SPLENDOUR trial was designed to evaluate whether the addition of denosumab to standard first-line platinum-based doublet chemotherapy improved OS in advanced NSCLC. Methods: Patients with stage IV NSCLC were randomized in a 1:1 ratio to either chemotherapy with or without denosumab (120 mg every 3–4 wks), stratified by the presence of bone metastases (at diagnosis), Eastern Cooperative Oncology Group performance status, histology, and region. To detect an OS increase from 9 to 11.25 months (hazard ratio [HR] = 0.80), 847 OS events were required. The trial closed prematurely owing to decreasing accrual rate. Results: A total of 514 patients were randomized, with 509 receiving one or more doses of the assigned treatment (chemotherapy: 252, chemotherapy-denosumab: 257). The median age was 66.1 years, 71% were men, and 59% were former smokers. Bone metastases were identified in 275 patients (53%). Median OS (95% confidence interval [CI]) was 8.7 (7.6–11.0) months in the control arm versus 8.2 (7.5–10.4) months in the chemotherapy-denosumab arm (HR = 0.96; 95% CI: 0.78–1.19; one-sided p = 0.36). For patients with bone metastasis, HR was 1.02 (95% CI: 0.77–1.35), whereas for those without, HR was 0.90 (95% CI: 0.66–1.23). Adverse events grade 3 or greater were observed in 40.9%, 5.2%, 8.7% versus 45.5%, 10.9%, 10.5% of patients. Conditional power for OS benefit was less than or equal to 10%. Conclusions: Denosumab was well-tolerated without unexpected safety concerns. There was no OS improvement for denosumab when added to chemotherapy in the intention-to-treat population and the subgroups with and without bone metastases. Our data do not provide evidence of a clinical benefit for denosumab in patients with NSCLC without bone metastases. © 2020 International Association for the Study of Lung Cancer

Published
2020

19. Evolution and Clinical Impact of EGFR Mutations in Circulating Free DNA in the BELIEF Trial

Author

Molina-Vila, M, Stahel, R, Dafni, U, Jordana-Ariza, N, Balada-Bel, A, Garzón-Ibáñez, M, García-Peláez, B, Mayo-de-Las-Casas, C, Felip, E, Fontecedro, A, Gautschi, O, Peters, S, Massutí, B, Palmero, R, Aix, S, Carcereny, E, Früh, M, Pless, M, Popat, S, Cuffe, S, Bidoli, P, Kammler, R, Roschitzki-Voser, H, Tsourti, Z, Karachaliou, N, Rosell, R, Molina-Vila, MA, Stahel, RA, Fontecedro, AC, Aix, SP, Molina-Vila, M, Stahel, R, Dafni, U, Jordana-Ariza, N, Balada-Bel, A, Garzón-Ibáñez, M, García-Peláez, B, Mayo-de-Las-Casas, C, Felip, E, Fontecedro, A, Gautschi, O, Peters, S, Massutí, B, Palmero, R, Aix, S, Carcereny, E, Früh, M, Pless, M, Popat, S, Cuffe, S, Bidoli, P, Kammler, R, Roschitzki-Voser, H, Tsourti, Z, Karachaliou, N, Rosell, R, Molina-Vila, MA, Stahel, RA, Fontecedro, AC, and Aix, SP

Abstract

Introduction: Longitudinal evaluation of mutations in blood samples was a prespecified secondary objective in the BELIEF trial of erlotinib and bevacizumab in advanced EGFR-positive NSCLC. Here, we report the testing results and explore the correlation of EGFR status in blood with clinical outcomes. Methods: Blood samples were prospectively collected from patients at baseline, at response evaluation, and at progression and sent to a central laboratory. Circulating free DNA was purified and EGFR mutations were analyzed with a validated real-time quantitative polymerase chain reaction assay. Results: EGFR exon 19/21 mutations were detected in 55 of 91 baseline blood samples (60.4%) and correlated with a significantly worse progression-free survival: 11.4 months (95% confidence interval [CI]: 9.0−14.8 mo) for the patients who were positive versus 22.9 months (95% CI: 9.5−33.9 mo) for those who were negative (log-rank p = 0.0020). Among the 74 samples at response, exon 19/21 mutations were detected only in three samples (4.1%). In contrast, 29 of 58 patients (50.0%) were exon 19/21 positive at progression and showed a significantly worse median overall survival of 21.7 months (95% CI: 17.0−30.9 mo) compared with 37.4 months (95% CI: 22.6−53.1 mo) for those who were negative (log-rank p = 0.011). Blood samples at the three time points were available for 48 patients. Of those, among 14 exon 19/21 EGFR-negative at presentation, 13 (93%) were persistently negative for the sensitizing mutations after progression and the p.T790M could only be detected in the blood of two patients. Conclusions: Longitudinal testing of EGFR mutations in blood can offer valuable clinical information. In patients of the BELIEF study, detection of EGFR mutations in circulating free DNA at presentation was associated with shorter progression-free survival, whereas positivity at progression correlated with shorter overall survival. Finally, patients negative in blood at presentation were almost inva

Published
2020

23. LBA51 KEYNOTE-024 5-year OS update: First-line (1L) pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) in patients (pts) with metastatic NSCLC and PD-L1 tumour proportion score (TPS) ≥50%

Author

Brahmer, J.R., primary, Rodriguez-Abreu, D., additional, Robinson, A.G., additional, Hui, R., additional, Csőszi, T., additional, Fülöp, A., additional, Gottfried, M., additional, Peled, N., additional, Tafreshi, A., additional, Cuffe, S., additional, O'Brien, M., additional, Rao, S., additional, Hotta, K., additional, Leal, T.A., additional, Riess, J.W., additional, Jensen, E., additional, Zhao, B., additional, Pietanza, M.C., additional, and Reck, M., additional

Published
2020
Full Text
View/download PDF

25. OA14.01 KEYNOTE-024 3-Year Survival Update: Pembrolizumab vs Platinum-Based Chemotherapy for Advanced Non–Small-Cell Lung Cancer

Author

Reck, M., primary, Rodríguez-Abreu, D., additional, Robinson, A.G., additional, Hui, R., additional, Csőszi, T., additional, Fülöp, A., additional, Gottfried, M., additional, Peled, N., additional, Tafreshi, A., additional, Cuffe, S., additional, O'Brien, M., additional, Rao, S., additional, Hotta, K., additional, Garay, T., additional, Jensen, E., additional, Ebiana, V., additional, and Brahmer, J.R., additional

Published
2019
Full Text
View/download PDF

27. Randomized Phase III Trial of Erlotinib versus Docetaxel in Patients with Advanced Squamous Cell Non-Small Cell Lung Cancer Failing First-Line Platinum-Based Doublet Chemotherapy Stratified by VeriStrat Good versus VeriStrat Poor. The European Thoracic Oncology Platform (ETOP) EMPHASIS-lung Trial

Author

Peters S, Stahel RA, Dafni U, Ponce Aix S, Massutí B, Gautschi O, Coate L, López Martín A, van Heemst R, Berghmans T, Meldgaard P, Cobo Dols M, Garde Noguera J, Curioni-Fontecedro A, Rauch D, Mark MT, Cuffe S, Biesma B, van Henten AMJ, Juan Vidal Ó, Palmero Sanchez R, Villa Guzmán JC, Collado Martin R, Peralta S, Insa A, Summers Y, Láng I, Horgan A, Ciardiello F, de Hosson S, Pieterman R, Groen HJM, van den Berg PM, Zielinski CC, Chittazhathu Kurian Kuruvilla Y, Gasca-Ruchti A, Kassapian M, Novello S, Torri V, Tsourti Z, Gregorc V, Smit EF, EMPHASIS-lung Collaborative Group, Pulmonary medicine, CCA - Cancer Treatment and quality of life, Peters, S, Stahel, Ra, Dafni, U, Aix, Sp, Massutí, B, Gautschi, O, Coate, L, López Martín, A, Van Heemst, R, Berghmans, T, Meldgaard, P, Cobo Dols, M, Noguera, Jg, Curioni Fontecedro, A, Rauch, D, Mark, Mt, Cuffe, S, Biesma, B, Van Henten, Am, Vidal, Ój, Sanchez, Rp, Villa Guzmán, Jc, Martin, Rc, Peralta, S, Insa, A, Summers, Y, Láng, I, Horgan, A, Ciardiello, Fortunato, De Hosson, S, Pieterman, R, Groen, Hj, Van Den Berg, Pm, Zielinski, Cc, Kuruvilla, Yc, Gasca Ruchti, A, Kassapian, M, Novello, S, Torri, V, Tsourti, Z, Gregorc, V, Smit, Ef, and EMPHASIS lung collaborative, Group

Subjects
Oncology, Male, Lung Neoplasms, medicine.medical_treatment, Docetaxel, NSCLC, THERAPY, Squamous, Cohort Studies, RETROSPECTIVE ANALYSIS, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, 3RD-LINE, Antineoplastic Combined Chemotherapy Protocols, VeriStrat, 030212 general & internal medicine, Erlotinib Hydrochloride, ETOP, Prognosis, Survival Rate, Erlotinib, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, Taxoids, Veristrat, 2ND-LINE TREATMENT, medicine.drug, Pulmonary and Respiratory Medicine, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, Multicenter trial, medicine, TYROSINE KINASE INHIBITORS, Journal Article, Humans, Lung cancer, COMBINATION, Survival rate, neoplasms, METAANALYSIS, Aged, Neoplasm Staging, Platinum, Chemotherapy, business.industry, medicine.disease, respiratory tract diseases, business, GROWTH-FACTOR RECEPTOR, Follow-Up Studies
Abstract

Introduction: Docetaxel and erlotinib are registered second line treatments for wild-type EGFR NSCLC. Previous studies suggested a predictive value of the VeriStrat test in second line therapy of NSCLC, classifying patients as either VeriStrat good or VeriStrat poor. EMPHASIS-lung aimed at exploring this predictive effect in patients with squamous cell NSCLC. The trial closed prematurely because of low accrual and results from other trials. Our analysis includes an exploratory combined analysis with results from the PROSE trial.Methods: EMPHASIS-lung was a randomized phase III multicenter trial exploring the differential effect of second line erlotinib versus docetaxel on progression-free survival (PFS) in VeriStrat good versus VeriStrat poor patients with squamous cell NSCLC.Results: A total of 80 patients were randomized, with 72.5% categorized as VeriStrat good. Patient characteristics were balanced between VeriStrat status and treatment groups. The median PFS times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 4.1 and 1.6 months, respectively, versus 1.9 and 2.1 months, respectively, in the VeriStrat poor cohort. The median overall survival (OS) times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 7.8 and 8.4 months, respectively, and 4.4 and 5.2 months, respectively, in the VeriStrat poor cohort. An additional exploratory analysis was performed; in it, 47 patients from the squamous cell subgroup of PROSE were included in a combined analysis, contributing with 45 PFS and 41 OS events.Conclusions: The final analysis of EMPHASIS-lung did not show a differential effect on PFS for erlotinib versus docetaxel stratified by VeriStrat status. Similarly, in the combined analysis, no significant treatment by VeriStrat status interaction was observed (interaction p=0.24 for PFS and 0.45 for OS, stratified by study). (C) 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Published
2016
Full Text
View/download PDF

28. Activated cMyc/PIM kinase promotes resistance to PI3K/mTOR inhibition in NSCLC

Author

Moore, G., Heavey, S., O'Byrne, K., Cuffe, S., Finn, S.P., O'Neill, M., Gately, K., Moore, G., Heavey, S., O'Byrne, K., Cuffe, S., Finn, S.P., O'Neill, M., and Gately, K.

Abstract

Therapeutically targeting the PI3K-mTOR pathway has shown promising clinical efficacy, however the inevitable emergence of drug resistance inhibits a durable response to treatment. We developed cell line models of acquired resistance to a PI3K-mTOR inhibitor Apitolisib following treatments with IC50 drug doses. Here we investigate the role the IL-6/STAT3 pathway contributes to PI3K-mTOR blockade resistance.

Published
2018

29. BBI608, a small molecule stemness inhibitor, packs a big punch against cisplatin resistant NSCLC

Author

MacDonagh, L., Gray, S.G., Cuffe, S., Finn, S.P., O?Byrne, K., Barr, M.P., MacDonagh, L., Gray, S.G., Cuffe, S., Finn, S.P., O?Byrne, K., and Barr, M.P.

Abstract

The cancer stem cell (CSC) hypothesis is a widely investigated field within oncology, it hypothesises that there is a robustly resistant stem-like population of cells that survive and thrive in initial chemotherapeutic treatment. These surviving CSCs contribute to the recapitulation of a heterogeneous tumour resulting in relapse and resistance. BBI608 is a small molecule inhibitor of cancer stemness, targeting STAT3, leading to the inhibition of critical genes required for the cancer stemness maintenance. Following the initial in vitro and in vivo preclinical promise of BBI608, phase II and III clinical trials are underway to investigate BBI608 in advanced malignancies and in combination with numerous chemotherapies.

Published
2018

30. Is miR-34a the micromanager of cancer stemness and resistance in NSCLC?

Author

MacDonagh, L., Gray, S.G., Gallagher, M., French, B., Gasch, C., Finn, S.P., Cuffe, S., O?Byrne, K., Barr, M.P., MacDonagh, L., Gray, S.G., Gallagher, M., French, B., Gasch, C., Finn, S.P., Cuffe, S., O?Byrne, K., and Barr, M.P.

Abstract

The capacity of microRNAs to post-transcriptionally regulate a myriad of genes has extended their remit into the realm of cancer stemness regulation. Disruption of Dicer-1, a crucial component of microRNA biogenesis, has been shown to completely deplete the stem cell pool in early development, indicating a potential role for microRNAs in the maintenance of stem cells. Such logic has led microRNAs to be investigated in the context of cancer stem cells (CSCs). Studies have revealed that microRNAs play a role in CSC self-renewal, differentiation, drug resistance and metastasis. With this, we hypothesise that microRNAs associated with cisplatin resistance and CSC maintenance may be key in targeting the CSC root of cisplatin resistance.

Published
2018

31. Big applications for a microRNA signature: the diagnostic, prognostic and predictive biomarker potential of a novel 5-miR signature associated with cisplatin resistant NSCLC

Author

MacDonagh, L., Gray, S.G., Gallagher, M., French, B., Gasch, C., Young, V., Ryan, R., Nicholson, S., Leonard, N., Finn, S.P., Cuffe, S., O?Byrne, K., Barr, M.P., MacDonagh, L., Gray, S.G., Gallagher, M., French, B., Gasch, C., Young, V., Ryan, R., Nicholson, S., Leonard, N., Finn, S.P., Cuffe, S., O?Byrne, K., and Barr, M.P.

Abstract

MicroRNAs are a class of small non-coding RNAs that range in size from 19–25 nucleotides. They have been shown to regulate a number of processes within tumour biology, including metastasis, invasion and angiogenesis. More recently, miRNAs have been linked to chemoresistance in solid tumours, including lung cancer. Their role in cisplatin resistance and their potential as biomarkers has yet to be determined.

Published
2018

32. A carrot a day keeps recurrence away! The use of vitamin A and its metabolic products in the circumvention of cisplatin resistance via Aldehyde Dehydrogenase 1 (ALDH1)

Author

MacDonagh, L., Gray, S.G., Gallagher, M., French, B., Gasch, C., Finn, S.P., Cuffe, S., O?Byrne, K., Barr, M.P., MacDonagh, L., Gray, S.G., Gallagher, M., French, B., Gasch, C., Finn, S.P., Cuffe, S., O?Byrne, K., and Barr, M.P.

Abstract

Despite advances in personalised medicine, cisplatin remains the mainstay in NSCLC management, however the develop-ment of pan-resistance to platinum agents has become a major clinical challenge. Novel drug design, preclinical and clinical trials working toward the approval of new drugs is a lengthy and costly process and in the interim research has turned its focus to overcoming resistance and repurposing drugs. Cancer stem cells (CSCs) have been hypothesised to be the initiating cells of resistance and recurrence. ALDH1-positive cells have been identified as a CSC subpopulation within cisplatin resistant (CisR) NSCLC sublines. ALDH1 converts retinal to retinoic acid during the metabolism of retinol (vitamin A), retinoic acid induces cell differentiation. All-trans retinoic acid (ATRA) is a well-established chemotherapeutic agent in the treatment of acute promyelocytic leukaemia; it induces the terminal differentiation of immature cells. We hypothesise that retinol and ATRA will deplete the ALDH1-positive CSC population thereby increasing or restoring cisplatin sensitivity.

Published
2018

33. In with the old! Repurposing disulfiram to target cancer stem cells (CSCs) and the root of cisplatin resistance

Author

MacDonagh, L., Gray, S.G., Cuffe, S., Finn, S.P., Nicholson, S., Ryan, R., Young, V., Leonard, N., O?Byrne, K., Barr, M.P., MacDonagh, L., Gray, S.G., Cuffe, S., Finn, S.P., Nicholson, S., Ryan, R., Young, V., Leonard, N., O?Byrne, K., and Barr, M.P.

Abstract

Cisplatin remains the cornerstone of NSCLC management. Despite initial sensitivity tumours develop resistance, undermining the cytotoxic effect of cisplatin. Numerous mechanisms have been investigated in terms of cisplatin resistance and its development, however, the clinical issue of resistance remains. An avenue of interest is the CSC hypothesis, in which the survival and expansion of highly resistant CSCs during chemotherapy are thought to be a contributing factor of resistance. Specific inhibition of key CSC markers in combination with chemotherapy may subvert the inherent resistance of the CSCs thereby restoring therapeutic effeciency. One such CSC marker is aldehyde dehydrogenase 1 (ALDH1). We hypothesise that inhibition of the ALDH1-positive CSCs within cispaltin resistant NSCLC will resensitise the cells to cisplatin.

Published
2018

34. Randomized Phase III Trial of Erlotinib versus Docetaxel in Patients with Advanced Squamous Cell Non–Small Cell Lung Cancer Failing First-Line Platinum-Based Doublet Chemotherapy Stratified by VeriStrat Good versus VeriStrat Poor. The European Thoracic Oncology Platform (ETOP) EMPHASIS-lung Trial

Author

Peters, S. Stahel, R.A. Dafni, U. Ponce Aix, S. Massutí, B. Gautschi, O. Coate, L. López Martín, A. van Heemst, R. Berghmans, T. Meldgaard, P. Cobo Dols, M. Garde Noguera, J. Curioni-Fontecedro, A. Rauch, D. Mark, M.T. Cuffe, S. Biesma, B. van Henten, A.M.J. Juan Vidal, Ó. Palmero Sanchez, R. Villa Guzmán, J.C. Collado Martin, R. Peralta, S. Insa, A. Summers, Y. Láng, I. Horgan, A. Ciardiello, F. de Hosson, S. Pieterman, R. Groen, H.J.M. van den Berg, P.M. Zielinski, C.C. Chittazhathu Kurian Kuruvilla, Y. Gasca-Ruchti, A. Kassapian, M. Novello, S. Torri, V. Tsourti, Z. Gregorc, V. Smit, E.F. EMPHASIS-lung Collaborative Group

Subjects
neoplasms, respiratory tract diseases
Abstract

Introduction Docetaxel and erlotinib are registered second-line treatments for wild-type EGFR NSCLC. Previous studies suggested a predictive value of the VeriStrat test in second-line therapy of NSCLC, classifying patients as either VeriStrat good or VeriStrat poor. EMPHASIS-lung aimed at exploring this predictive effect in patients with squamous cell NSCLC. The trial closed prematurely because of low accrual and results from other trials. Our analysis includes an exploratory combined analysis with results from the PROSE trial. Methods EMPHASIS-lung was a randomized phase III multicenter trial exploring the differential effect of second-line erlotinib versus docetaxel on progression-free survival (PFS) in VeriStrat good versus VeriStrat poor patients with squamous cell NSCLC. Results A total of 80 patients were randomized, with 72.5% categorized as VeriStrat good. Patient characteristics were balanced between VeriStrat status and treatment groups. The median PFS times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 4.1 and 1.6 months, respectively, versus 1.9 and 2.1 months, respectively, in the VeriStrat poor cohort. The median overall survival (OS) times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 7.8 and 8.4 months, respectively, and 4.4 and 5.2 months, respectively, in the VeriStrat poor cohort. An additional exploratory analysis was performed; in it, 47 patients from the squamous cell subgroup of PROSE were included in a combined analysis, contributing with 45 PFS and 41 OS events. Conclusions The final analysis of EMPHASIS-lung did not show a differential effect on PFS for erlotinib versus docetaxel stratified by VeriStrat status. Similarly, in the combined analysis, no significant treatment by VeriStrat status interaction was observed (interaction p = 0.24 for PFS and 0.45 for OS, stratified by study). © 2017 International Association for the Study of Lung Cancer

Published
2017

35. Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer and activating EGFR mutations (BELIEF): an international, multicentre, single-arm, phase 2 trial

Author

Rosell, R, Dafni, U, Felip, E, Curioni-Fontecedro, A, Gautschi, O, Peters, S, Massuti, B, Palmero, R, Aix, SP, Carcereny, E, Fruh, M, Pless, M, Popat, S, Kotsakis, A, Cuffe, S, Bidoli, P, Favaretto, A, Froesch, P, Reguart, N, Puente, J, Coate, L, Barlesi, F, Rauch, D, Thomas, M, Camps, C, Gomez-Codina, J, Majem, M, Porta, R, Shah, R, Hanrahan, E, Kammler, R, Ruepp, B, Rabaglio, M, Kassapian, M, Karachaliou, N, Tam, R, Shames, DS, Molina-Vila, MA, Stahel, RA, and BELIEF collaborative group

Subjects
respiratory tract diseases
Abstract

BACKGROUND: The tyrosine kinase inhibitor erlotinib improves the outcomes of patients with advanced non-small-cell lung carcinoma (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations. The coexistence of the T790M resistance mutation with another EGFR mutation in treatment-naive patients has been associated with a shorter progression-free survival to EGFR inhibition than in the absence of the T790M mutation. To test this hypothesis clinically, we developed a proof-of-concept study, in which patients with EGFR-mutant NSCLC were treated with the combination of erlotinib and bevacizumab, stratified by the presence of the pretreatment T790M mutation. METHODS: BELIEF was an international, multicentre, single-arm, phase 2 trial done at 29 centres in eight European countries. Eligible patients were aged 18 years or older and had treatment-naive, pathologically confirmed stage IIIB or stage IV lung adenocarcinoma with a confirmed, activating EGFR mutation (exon 19 deletion or L858R mutation). Patients received oral erlotinib 150 mg per day and intravenous bevacizumab 15 mg/kg every 21 days and were tested centrally for the pretreatment T790M resistance mutation with a peptide nucleic acid probe-based real-time PCR. The primary endpoint was progression-free survival. The primary efficacy analysis was done in the intention-to-treat population and was stratified into two parallel substudies according to the centrally confirmed pretreatment T790M mutation status of enrolled patients (T790M positive or negative). The safety analysis was done in all patients that have received at least one dose of trial treatment. This trial was registered with ClinicalTrials.gov, number NCT01562028. FINDINGS: Between June 11, 2012, and Oct 28, 2014, 109 patients were enrolled and included in the efficacy analysis. 37 patients were T790M mutation positive and 72 negative. The overall median progression-free survival was 13·2 months (95% CI 10·3-15·5), with a 12 month progression-free survival of 55% (95% CI 45-64). The primary endpoint was met only in substudy one (T790M-positive patients). In the T790M-positive group, median progression-free survival was 16·0 months (12·7 to not estimable), with a 12 month progression-free survival of 68% (50-81), whereas in the T790M-negative group, median progression-free survival was 10·5 months (9·4-14·2), with a 12 month progression-free survival of 48% (36-59). Of 106 patients included in the safety analysis, five had grade 4 adverse events (one acute coronary syndrome, one biliary tract infection, one other neoplasms, and two colonic perforations) and one died due to sepsis. INTERPRETATION: The BELIEF trial provides further evidence of benefit for the combined use of erlotinib and bevacizumab in patients with NSCLC harbouring activating EGFR mutations. FUNDING: European Thoracic Oncology Platform, Roche.

Published
2017

36. Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer and activating EGFR mutations (BELIEF): an international, multicentre, single-arm, phase 2 trial

Author

Rosell, R. Dafni, U. Felip, E. Curioni-Fontecedro, A. Gautschi, O. Peters, S. Massutí, B. Palmero, R. Aix, S.P. Carcereny, E. Früh, M. Pless, M. Popat, S. Kotsakis, A. Cuffe, S. Bidoli, P. Favaretto, A. Froesch, P. Reguart, N. Puente, J. Coate, L. Barlesi, F. Rauch, D. Thomas, M. Camps, C. Gómez-Codina, J. Majem, M. Porta, R. Shah, R. Hanrahan, E. Kammler, R. Ruepp, B. Rabaglio, M. Kassapian, M. Karachaliou, N. Tam, R. Shames, D.S. Molina-Vila, M.A. Stahel, R.A. BELIEF collaborative group

Subjects
respiratory tract diseases
Abstract

Background The tyrosine kinase inhibitor erlotinib improves the outcomes of patients with advanced non-small-cell lung carcinoma (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations. The coexistence of the T790M resistance mutation with another EGFR mutation in treatment-naive patients has been associated with a shorter progression-free survival to EGFR inhibition than in the absence of the T790M mutation. To test this hypothesis clinically, we developed a proof-of-concept study, in which patients with EGFR-mutant NSCLC were treated with the combination of erlotinib and bevacizumab, stratified by the presence of the pretreatment T790M mutation. Methods BELIEF was an international, multicentre, single-arm, phase 2 trial done at 29 centres in eight European countries. Eligible patients were aged 18 years or older and had treatment-naive, pathologically confirmed stage IIIB or stage IV lung adenocarcinoma with a confirmed, activating EGFR mutation (exon 19 deletion or L858R mutation). Patients received oral erlotinib 150 mg per day and intravenous bevacizumab 15 mg/kg every 21 days and were tested centrally for the pretreatment T790M resistance mutation with a peptide nucleic acid probe-based real-time PCR. The primary endpoint was progression-free survival. The primary efficacy analysis was done in the intention-to-treat population and was stratified into two parallel substudies according to the centrally confirmed pretreatment T790M mutation status of enrolled patients (T790M positive or negative). The safety analysis was done in all patients that have received at least one dose of trial treatment. This trial was registered with ClinicalTrials.gov, number NCT01562028. Findings Between June 11, 2012, and Oct 28, 2014, 109 patients were enrolled and included in the efficacy analysis. 37 patients were T790M mutation positive and 72 negative. The overall median progression-free survival was 13·2 months (95% CI 10·3–15·5), with a 12 month progression-free survival of 55% (95% CI 45–64). The primary endpoint was met only in substudy one (T790M-positive patients). In the T790M-positive group, median progression-free survival was 16·0 months (12·7 to not estimable), with a 12 month progression-free survival of 68% (50–81), whereas in the T790M-negative group, median progression-free survival was 10·5 months (9·4–14·2), with a 12 month progression-free survival of 48% (36–59). Of 106 patients included in the safety analysis, five had grade 4 adverse events (one acute coronary syndrome, one biliary tract infection, one other neoplasms, and two colonic perforations) and one died due to sepsis. Interpretation The BELIEF trial provides further evidence of benefit for the combined use of erlotinib and bevacizumab in patients with NSCLC harbouring activating EGFR mutations. Funding European Thoracic Oncology Platform, Roche. © 2017 Elsevier Ltd

Published
2017

39. Evolution and clinical impact of EGFR mutations in circulating free DNA in the BELIEF trial

Author

Curioni, A., primary, Felip, E., additional, Dafni, U., additional, Molina, M.-A., additional, Gautschi, O., additional, Peters, S., additional, Massutí, B., additional, Palmero, R., additional, Ponce, S., additional, Carcereny, E., additional, Früh, M., additional, Pless, M., additional, Popat, S., additional, Cuffe, S., additional, Karachaliou, N., additional, Kammler, R., additional, Kassapian, M., additional, Roschitzki-Voser, H., additional, Stahel, R.A., additional, and Rosell, R., additional

Published
2018
Full Text
View/download PDF

40. PS3 KEYNOTE-024 Update: Pembrolizumab vs Platinum-Based Chemotherapy for Advanced NSCLC with PD-L1 Tumor Proportion Score ≥50%

Author

Brahmer, J., primary, Rodríguez-Abreu, D., additional, Robinson, A., additional, Hui, R., additional, Csőszi, T., additional, Fülöp, A., additional, Gottfried, M., additional, Peled, N., additional, Tafreshi, A., additional, Cuffe, S., additional, O'Brien, M., additional, Rao, S., additional, Hotta, K., additional, Riccio, A., additional, Yang, J., additional, Pietanza, M.C., additional, and Reck, M., additional

Published
2018
Full Text
View/download PDF

46. Big applications for a microRNA signature: the diagnostic, prognostic and predictive biomarker potential of a novel 5-miR signature associated with cisplatin resistant NSCLC

Author

MacDonagh, L., primary, Gray, S.G., additional, Gallagher, M., additional, French, B., additional, Gasch, C., additional, Young, V., additional, Ryan, R., additional, Nicholson, S., additional, Leonard, N., additional, Finn, S.P., additional, Cuffe, S., additional, O’Byrne, K., additional, and Barr, M.P., additional

Published
2018
Full Text
View/download PDF

50. 2: XRCC6BP1: A key player in cisplatin resistance and lung cancer stem cells

Author

Barr, M.P., Singh, S., Foley, E., He, Y., Young, V., Ryan, R., Nicholson, S., Leonard, N., O'Byrne, K.J., Cuffe, S., Finn, S., Barr, M.P., Singh, S., Foley, E., He, Y., Young, V., Ryan, R., Nicholson, S., Leonard, N., O'Byrne, K.J., Cuffe, S., and Finn, S.

Abstract

Alterations in the DNA repair capacity of damaged cells is now recognised as an important factor in mediating resistance to chemotherapeutic agents.

Published
2017

Catalog

Books, media, physical & digital resources
See catalog results