Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer
Patrick M Forde, Jonathan Spicer, Shun Lu, Mariano Provencio, Tetsuya Mitsudomi, Mark M Awad, Enriqueta Felip, Stephen R Broderick, Julie R Brahmer, Scott J Swanson, Keith Kerr, Changli Wang, Tudor-Eliade Ciuleanu, Gene B Saylors, Fumihiro Tanaka, Hiroyuki Ito, Ke-Neng Chen, Moishe Liberman, Everett E Vokes, Janis M Taube, Cecile Dorange, Junliang Cai, Joseph Fiore, Anthony Jarkowski, David Balli, Mark Sausen, Dimple Pandya, Christophe Y Calvet, Nicolas Girard, CheckMate 816 Investigators, Lorena Lupinacci, Claudio Martin, Carlos Barrios, Fabio Franke, Rodrigo Medeiros, Andre Murad, Moishe Liberman, Jonathan Spicer, Shelly Sud, Sunil Yadav, Ke-Neng Chen, Qixun Chen, Junke Fu, Yi Hu, Xiaofei Li, Jichun Liu, Lunxu Liu, Shun Lu, Changli Wang, Qun Wang, Wenxiang Wang, Lin Wu, Kejing Ying, Chunfang Zhang, Jian Zhao, Nicolas Girard, Herve Lena, Julien Mazieres, Bertrand Mennecier, Eric Pichon, Pierre Jean Souquet, Gerard Zalcman, Sofia Baka, Elisa Bennicelli, Federico Cappuzzo, Manolo D'Arcangelo, Domenico Galetta, Vincenzo Minotti, Shinji Atagi, Norihiko Ikeda, Hiroyuki Ito, Kaoru Kubota, Tetsuya Mitsudomi, Yasuhisa Ohde, Satoshi Oizumi, Morihito Okada, Jiro Okami, Noriaki Sakakura, Yutaka Shio, Shunichi Sugawara, Kazuya Takamochi, Fumihiro Tanaka, Keisuke Tomii, Masahiro Tsuboi, Tae Won Jang, Young-Chul Kim, Sung Yong Lee, Aurelia Alexandru, Tudor Ciuleanu, Enriqueta Felip, Mariano Provencio Pulla, Chao-Hua Chiu, Kai-Ling Lee, Kang-Yun Lee, Tsung-Ying Yang, Timucin Cil, Ahmet Demirkazik, Zeynep Turna, Wallace Akerley, Warren Alexander, Mark Awad, Hossein Borghaei, Brian Byrne, Jeremy Cetnar, Jason Chesney, Makenzi Evangelist, Patrick Forde, Abhimanyu Ghose, Vallathucherry Harish, Harry Harper, Thomas Harris, Leora Horn, John Hrom, Wade Thomas Iams, Arielle Lee, Giberto Lopes, Nisha Mohindra, Timothy O'Brien, Krishna Pachipala, Andrew Popoff, Suman Rao, Ahad Sadiq, Gene Saylors, Lasika Seneviratne, Elaine Shum, David Spigel, Sarah Cannon, Alexander Spira, James Uyeki, Christopher Vaughn, John Villano, Everett Vokes, Benny Weksler, John Wrangle, Robert A Anders, Alexander S Baras, Jonathan D Cuda, Jaroslaw Jedrych, Ashley Cimino-Mathews, Edward Gabrielson, Peter B Illei, Julie E Stein, Janis M Taube, Elizabeth D Thompson, Daphne Wang, Patrick M Forde, Jonathan Spicer, Shun Lu, Mariano Provencio, Tetsuya Mitsudomi, Mark M Awad, Enriqueta Felip, Stephen R Broderick, Julie R Brahmer, Scott J Swanson, Keith Kerr, Changli Wang, Tudor-Eliade Ciuleanu, Gene B Saylors, Fumihiro Tanaka, Hiroyuki Ito, Ke-Neng Chen, Moishe Liberman, Everett E Vokes, Janis M Taube, Cecile Dorange, Junliang Cai, Joseph Fiore, Anthony Jarkowski, David Balli, Mark Sausen, Dimple Pandya, Christophe Y Calvet, Nicolas Girard, CheckMate 816 Investigators, Lorena Lupinacci, Claudio Martin, Carlos Barrios, Fabio Franke, Rodrigo Medeiros, Andre Murad, Moishe Liberman, Jonathan Spicer, Shelly Sud, Sunil Yadav, Ke-Neng Chen, Qixun Chen, Junke Fu, Yi Hu, Xiaofei Li, Jichun Liu, Lunxu Liu, Shun Lu, Changli Wang, Qun Wang, Wenxiang Wang, Lin Wu, Kejing Ying, Chunfang Zhang, Jian Zhao, Nicolas Girard, Herve Lena, Julien Mazieres, Bertrand Mennecier, Eric Pichon, Pierre Jean Souquet, Gerard Zalcman, Sofia Baka, Elisa Bennicelli, Federico Cappuzzo, Manolo D'Arcangelo, Domenico Galetta, Vincenzo Minotti, Shinji Atagi, Norihiko Ikeda, Hiroyuki Ito, Kaoru Kubota, Tetsuya Mitsudomi, Yasuhisa Ohde, Satoshi Oizumi, Morihito Okada, Jiro Okami, Noriaki Sakakura, Yutaka Shio, Shunichi Sugawara, Kazuya Takamochi, Fumihiro Tanaka, Keisuke Tomii, Masahiro Tsuboi, Tae Won Jang, Young-Chul Kim, Sung Yong Lee, Aurelia Alexandru, Tudor Ciuleanu, Enriqueta Felip, Mariano Provencio Pulla, Chao-Hua Chiu, Kai-Ling Lee, Kang-Yun Lee, Tsung-Ying Yang, Timucin Cil, Ahmet Demirkazik, Zeynep Turna, Wallace Akerley, Warren Alexander, Mark Awad, Hossein Borghaei, Brian Byrne, Jeremy Cetnar, Jason Chesney, Makenzi Evangelist, Patrick Forde, Abhimanyu Ghose, Vallathucherry Harish, Harry Harper, Thomas Harris, Leora Horn, John Hrom, Wade Thomas Iams, Arielle Lee, Giberto Lopes, Nisha Mohindra, Timothy O'Brien, Krishna Pachipala, Andrew Popoff, Suman Rao, Ahad Sadiq, Gene Saylors, Lasika Seneviratne, Elaine Shum, David Spigel, Sarah Cannon, Alexander Spira, James Uyeki, Christopher Vaughn, John Villano, Everett Vokes, Benny Weksler, John Wrangle, Robert A Anders, Alexander S Baras, Jonathan D Cuda, Jaroslaw Jedrych, Ashley Cimino-Mathews, Edward Gabrielson, Peter B Illei, Julie E Stein, Janis M Taube, Elizabeth D Thompson, Daphne Wang
Abstract
Background: Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings.
Methods: In this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients.
Results: The median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-plus-chemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group.
Conclusions: In patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.).
Copyright © 2022 Massachusetts Medical Society.
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Source: PubMed