Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer
Scott J Antonia, Augusto Villegas, Davey Daniel, David Vicente, Shuji Murakami, Rina Hui, Takashi Yokoi, Alberto Chiappori, Ki H Lee, Maike de Wit, Byoung C Cho, Maryam Bourhaba, Xavier Quantin, Takaaki Tokito, Tarek Mekhail, David Planchard, Young-Chul Kim, Christos S Karapetis, Sandrine Hiret, Gyula Ostoros, Kaoru Kubota, Jhanelle E Gray, Luis Paz-Ares, Javier de Castro Carpeño, Catherine Wadsworth, Giovanni Melillo, Haiyi Jiang, Yifan Huang, Phillip A Dennis, Mustafa Özgüroğlu, PACIFIC Investigators, Kevin Jasas, Kenneth Obyrne, Baerin Houghton, Brett Hughes, Craig Lewis, Matthew Links, Say Ng, Phillip Parente, Stanislaw Gauden, Frederic Forget, Piet Vercauter, Johan Vansteenkiste, Jean-Luc Canon, Parnet Cheema, Mark Vincent, Nevin Murray, Jeffrey Rothenstein, Labib Zibdawi, Penelope Bradbury, Charles Butts, Robert El-Maraghi, Dafydd Bebb, Alejandro Acevedo Gaete, Eric Armando Orellana Ulunque, Osvaldo Rudy Aren Frontera, Julien Mazières, Patrick Aldo Renault, Gilles Robinet, Alexis Cortot, Werner Hilgers, Michel Poudenx, Fabrice Barlesi, Claude El Kouri, Maurice Perol, Hervé Lena, Marielle Sabatini, Jean-Louis Pujol, Eckart Laack, Christian Schulz, Wolfram Brugger, Martin Faehling, Martin Reck, Thomas Wolff, Juergen Fischer, Till-Oliver Emde, Christian Scholz, Anja Rueckert, Haralabos Kalofonos, Athanasios Kotsakis, Konstantinos Syrigos, Konstantinos Papazisis, Kostantinos Zarogoulidis, Zsuzsanna Sztancsik, Gyorgy Losonczy, Eszter Csanky, Hovav Nechushtan, Mirjana Wollner, Antonio Chella, Alessandra Bearz, Vincenzo Emanuele Chiuri, Marina Garassino, Luca Gianni, Matteo Brighenti, Fortunato Ciardiello, Michele Milella, Hector Soto Parra, Shunichi Sugawara, Shinji Atagi, Tomonori Hirashima, Fumio Imamura, Yasuo Iwamoto, Shintaro Kanda, Noriyuki Masuda, Koichi Minato, Kazuhiko Nakagawa, Seiji Niho, Hideo Saka, Toshiaki Takahashi, Yasuhito Fujisaka, Hiroshi Sakai, Kazuhisa Takahashi, Tomohisa Baba, Masao Harada, Kazuo Kasahara, Tadashi Maeda, Makoto Maemondo, Isamu Okamoto, Yuichiro Takeda, Kunihiko Kobayashi, Naoyuki Nogami, Katsuyuki Kiura, Terufumi Kato, Katsuyuki Hotta, Keunchil Park, Eun Kyung Cho, Hoon Kyo Kim, Jong-Seok Lee, Choonhee Son, Sang-We Kim, Sang-Won Shin, Joo-Hang Kim, Joop De Langen, Ben van den Borne, Jeroen Steven Kloover, Michael van den Heuvel, Kornelis Harm van der Leest, Joachim G J V Aerts, Sayed Hashemi, Wuilbert Rodriguez Pantigoso, Vanessa Bermudez Alfaro, Jacek Jassem, Slawomir Mandziuk, Dariusz Kowalski, Akhil Chopra, Eng Huat Tan, Tan Min Chin, Ross Andrew Soo, Marian Stresko, Pavol Demo, Tibor Packan, Jozef Chovanec, Graham Cohen, Conrad Jacobs, Daniel Rens, Jesus Corral Jaime, Oscar Juan Vidal, Alvaro Taus Garcia, Felipe Cardenal Alemany, Ramon Garcia Gomez, Esther Holgado Martin, Santiago Ponce Aix, Rut Porta Balanya, Dolores Isla Casado, Margarita Majem Tarruella, Diego Marquez Medina, Jesus Alfaro Lizaso, Ana Blasco Cordellat, Jose Miguel Sanchez Torres, Bartomeu Massuti Sureda, Amparo Sanchez, Cristobal Belda Iniesta, Rosa Alvarez, Te-Chun Hsia, Yuh-Min Chen, Kang-Yun Lee, Yung-Chang Lien, Chih-Hsin Yang, Chi-Li Chung, Thanyanan Reungwetwattana, Busayamas Chewaskulyong, Sarayut Lucien Geater, Tuncay Goksel, Hakan Harputluoglu, Mehmet Artac, Semra Paydas, Ozden Altundag, Orhan Sencan, Jonathan Hicks, Corinne Faivre-Finn, Toby Talbot, Bijoy Telivala, Maen Hussein, Michael McCLeod, Dennis Slater, James V H Uyeki, David Waterhouse, Franklin L Chen, Zhonglin Hao, Ronan Kelly, Daniel Morgensztern, Ray Page, Alexander I Spira, Mark Awad, Joseph Thaddeus Beck, Alan Richard Berg, Janak Choksi, Scott Dorroh, Jonathan Goldman, Nicholas Iannotti, Kendra Kubiak, Suman Rao, Arvind Chaudhry, Chirag J Dalsania, Nicholas J Farrell, Robert Hermann, Charles S Kuzma, Kristi J McIntyre, William Mitchell, Estelamari Rodriguez, Ashish Sangal, David A Smith, Kai Zu, Ian C Anderson, Deepti Behl, William J Edenfield, Hassan Ghazal, Giuseppe Giaccone, Christopher Thomas Hagenstad, Missak Haigentz Jr, Harry Harper, Charles Henderson, Borys Hrinczenko, Kartik Konduri, Marshall Levine, Danko Martincic, Rathi Narayana Pillai, Muhammad Salamat, Mikhail Shtivelband, Joginder Singh, Matei P Socoteanu, David Spigel, Paul Zorsky, Renata Ferrarotto, Jorge Gomez, Leora Horn, Stephan Kendall, William E Lawler, Leena Gandhi, Dylan Zylla, Vasileios Assikis, Steven McCune, Samuel Bailey, Anh Tuan Le, Khoa Mai, Luu Nguyen, Scott J Antonia, Augusto Villegas, Davey Daniel, David Vicente, Shuji Murakami, Rina Hui, Takashi Yokoi, Alberto Chiappori, Ki H Lee, Maike de Wit, Byoung C Cho, Maryam Bourhaba, Xavier Quantin, Takaaki Tokito, Tarek Mekhail, David Planchard, Young-Chul Kim, Christos S Karapetis, Sandrine Hiret, Gyula Ostoros, Kaoru Kubota, Jhanelle E Gray, Luis Paz-Ares, Javier de Castro Carpeño, Catherine Wadsworth, Giovanni Melillo, Haiyi Jiang, Yifan Huang, Phillip A Dennis, Mustafa Özgüroğlu, PACIFIC Investigators, Kevin Jasas, Kenneth Obyrne, Baerin Houghton, Brett Hughes, Craig Lewis, Matthew Links, Say Ng, Phillip Parente, Stanislaw Gauden, Frederic Forget, Piet Vercauter, Johan Vansteenkiste, Jean-Luc Canon, Parnet Cheema, Mark Vincent, Nevin Murray, Jeffrey Rothenstein, Labib Zibdawi, Penelope Bradbury, Charles Butts, Robert El-Maraghi, Dafydd Bebb, Alejandro Acevedo Gaete, Eric Armando Orellana Ulunque, Osvaldo Rudy Aren Frontera, Julien Mazières, Patrick Aldo Renault, Gilles Robinet, Alexis Cortot, Werner Hilgers, Michel Poudenx, Fabrice Barlesi, Claude El Kouri, Maurice Perol, Hervé Lena, Marielle Sabatini, Jean-Louis Pujol, Eckart Laack, Christian Schulz, Wolfram Brugger, Martin Faehling, Martin Reck, Thomas Wolff, Juergen Fischer, Till-Oliver Emde, Christian Scholz, Anja Rueckert, Haralabos Kalofonos, Athanasios Kotsakis, Konstantinos Syrigos, Konstantinos Papazisis, Kostantinos Zarogoulidis, Zsuzsanna Sztancsik, Gyorgy Losonczy, Eszter Csanky, Hovav Nechushtan, Mirjana Wollner, Antonio Chella, Alessandra Bearz, Vincenzo Emanuele Chiuri, Marina Garassino, Luca Gianni, Matteo Brighenti, Fortunato Ciardiello, Michele Milella, Hector Soto Parra, Shunichi Sugawara, Shinji Atagi, Tomonori Hirashima, Fumio Imamura, Yasuo Iwamoto, Shintaro Kanda, Noriyuki Masuda, Koichi Minato, Kazuhiko Nakagawa, Seiji Niho, Hideo Saka, Toshiaki Takahashi, Yasuhito Fujisaka, Hiroshi Sakai, Kazuhisa Takahashi, Tomohisa Baba, Masao Harada, Kazuo Kasahara, Tadashi Maeda, Makoto Maemondo, Isamu Okamoto, Yuichiro Takeda, Kunihiko Kobayashi, Naoyuki Nogami, Katsuyuki Kiura, Terufumi Kato, Katsuyuki Hotta, Keunchil Park, Eun Kyung Cho, Hoon Kyo Kim, Jong-Seok Lee, Choonhee Son, Sang-We Kim, Sang-Won Shin, Joo-Hang Kim, Joop De Langen, Ben van den Borne, Jeroen Steven Kloover, Michael van den Heuvel, Kornelis Harm van der Leest, Joachim G J V Aerts, Sayed Hashemi, Wuilbert Rodriguez Pantigoso, Vanessa Bermudez Alfaro, Jacek Jassem, Slawomir Mandziuk, Dariusz Kowalski, Akhil Chopra, Eng Huat Tan, Tan Min Chin, Ross Andrew Soo, Marian Stresko, Pavol Demo, Tibor Packan, Jozef Chovanec, Graham Cohen, Conrad Jacobs, Daniel Rens, Jesus Corral Jaime, Oscar Juan Vidal, Alvaro Taus Garcia, Felipe Cardenal Alemany, Ramon Garcia Gomez, Esther Holgado Martin, Santiago Ponce Aix, Rut Porta Balanya, Dolores Isla Casado, Margarita Majem Tarruella, Diego Marquez Medina, Jesus Alfaro Lizaso, Ana Blasco Cordellat, Jose Miguel Sanchez Torres, Bartomeu Massuti Sureda, Amparo Sanchez, Cristobal Belda Iniesta, Rosa Alvarez, Te-Chun Hsia, Yuh-Min Chen, Kang-Yun Lee, Yung-Chang Lien, Chih-Hsin Yang, Chi-Li Chung, Thanyanan Reungwetwattana, Busayamas Chewaskulyong, Sarayut Lucien Geater, Tuncay Goksel, Hakan Harputluoglu, Mehmet Artac, Semra Paydas, Ozden Altundag, Orhan Sencan, Jonathan Hicks, Corinne Faivre-Finn, Toby Talbot, Bijoy Telivala, Maen Hussein, Michael McCLeod, Dennis Slater, James V H Uyeki, David Waterhouse, Franklin L Chen, Zhonglin Hao, Ronan Kelly, Daniel Morgensztern, Ray Page, Alexander I Spira, Mark Awad, Joseph Thaddeus Beck, Alan Richard Berg, Janak Choksi, Scott Dorroh, Jonathan Goldman, Nicholas Iannotti, Kendra Kubiak, Suman Rao, Arvind Chaudhry, Chirag J Dalsania, Nicholas J Farrell, Robert Hermann, Charles S Kuzma, Kristi J McIntyre, William Mitchell, Estelamari Rodriguez, Ashish Sangal, David A Smith, Kai Zu, Ian C Anderson, Deepti Behl, William J Edenfield, Hassan Ghazal, Giuseppe Giaccone, Christopher Thomas Hagenstad, Missak Haigentz Jr, Harry Harper, Charles Henderson, Borys Hrinczenko, Kartik Konduri, Marshall Levine, Danko Martincic, Rathi Narayana Pillai, Muhammad Salamat, Mikhail Shtivelband, Joginder Singh, Matei P Socoteanu, David Spigel, Paul Zorsky, Renata Ferrarotto, Jorge Gomez, Leora Horn, Stephan Kendall, William E Lawler, Leena Gandhi, Dylan Zylla, Vasileios Assikis, Steven McCune, Samuel Bailey, Anh Tuan Le, Khoa Mai, Luu Nguyen
Abstract
Background: Most patients with locally advanced, unresectable, non-small-cell lung cancer (NSCLC) have disease progression despite definitive chemoradiotherapy (chemotherapy plus concurrent radiation therapy). This phase 3 study compared the anti-programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy.
Methods: We randomly assigned patients, in a 2:1 ratio, to receive durvalumab (at a dose of 10 mg per kilogram of body weight intravenously) or placebo every 2 weeks for up to 12 months. The study drug was administered 1 to 42 days after the patients had received chemoradiotherapy. The coprimary end points were progression-free survival (as assessed by means of blinded independent central review) and overall survival (unplanned for the interim analysis). Secondary end points included 12-month and 18-month progression-free survival rates, the objective response rate, the duration of response, the time to death or distant metastasis, and safety.
Results: Of 713 patients who underwent randomization, 709 received consolidation therapy (473 received durvalumab and 236 received placebo). The median progression-free survival from randomization was 16.8 months (95% confidence interval [CI], 13.0 to 18.1) with durvalumab versus 5.6 months (95% CI, 4.6 to 7.8) with placebo (stratified hazard ratio for disease progression or death, 0.52; 95% CI, 0.42 to 0.65; P<0.001); the 12-month progression-free survival rate was 55.9% versus 35.3%, and the 18-month progression-free survival rate was 44.2% versus 27.0%. The response rate was higher with durvalumab than with placebo (28.4% vs. 16.0%; P<0.001), and the median duration of response was longer (72.8% vs. 46.8% of the patients had an ongoing response at 18 months). The median time to death or distant metastasis was longer with durvalumab than with placebo (23.2 months vs. 14.6 months; P<0.001). Grade 3 or 4 adverse events occurred in 29.9% of the patients who received durvalumab and 26.1% of those who received placebo; the most common adverse event of grade 3 or 4 was pneumonia (4.4% and 3.8%, respectively). A total of 15.4% of patients in the durvalumab group and 9.8% of those in the placebo group discontinued the study drug because of adverse events.
Conclusions: Progression-free survival was significantly longer with durvalumab than with placebo. The secondary end points also favored durvalumab, and safety was similar between the groups. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461 .).
Source: PubMed