SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
2023; Elsevier BV; Volume: 35; Issue: 1 Linguagem: Inglês
10.1016/j.annonc.2023.10.004
ISSN1569-8041
AutoresHossein Borghaei, Filippo de Marinis, Daphne W. Dumoulin, Craig H. Reynolds, Willemijn S.M.E. Theelen, Ivor Percent, V. Gutiérrez Calderón, Melissa L. Johnson, Anne Madroszyk, Edward B. Garon, Kai He, David Planchard, Martin Reck, Sanjay Popat, Roy S. Herbst, Ticiana Leal, Ronald Shazer, Xin Yan, Richard Harrigan, Solange Peters, Isam Abdel-Karim, Mahmoud Abdelsalam, Alfredo Addeo, Carlos Aguado, Patrick Alexander, Jürgen Alt, Georges Azzi, Rama Balaraman, Bonne Biesma, Fiona Blackhall, Sabine Bohnet, Ekaterini Boleti, Hossein Borghaei, Penelope A. Bradbury, Matteo Brighenti, Nicholas Campbell, Toby Campbell, Jean-Luc Canon, Federico Cappuzzo, Enric Carcereny, Luigi Cavanna, Jeremy Cetnar, Antonio Chella, C. Chouaïd, Daniel C. Christoph, J. Cortés Castán, Shaker R. Dakhil, F.J. de Castro Carpeño, Filippo de Marinis, Angelo Delmonte, Ingel Demedts, Wim Demey, Joyce Dits, Maria del Pilar Diz Taín, M. Dómine Gómez, Timothy Dorius, Daphne W. Dumoulin, M. Duruisseaux, Keith D. Eaton, Emilio Esteban, Devon Evans, Martin Faehling, Nicholas Farrell, Trevor Feinstein, E. Felip Font, M.R. García Campelo, Edward B. Garon, Pilar Garrido, Paul Germonpré, Todd Gersten, María González Cao, Srivalli Gopaluni, Laurent Greillier, Francesco Grossi, Florian Guisier, Sarada Gurubhagavatula, Vanesa Gutiérrez Calderón, David Hakimian, Richard D. Hall, Desirée Hao, Ronald Harris, Sayed M.S. Hashemi, Kai He, Lizza Hendriks, Chao Huang, Emad Ibrahim, Sharad Jain, Melissa L. Johnson, B. J. P. Jones, Monte Jones, Óscar Juan, Rosalyn A. Juergens, Courèche Kaderbhaï, Elisabeth A. Kastelijn, Roger Keresztes, Ebenezer A. Kio, Konrad Kokowski, Kartik Konduri, Swati Kulkarni, Jonas Kuon, Carla Kurkjian, Catherine Labbé, Rachel E. Lerner, Farah Louise Lim, Anne Madroszyk, Omkar Marathe, Danko Martincic, Edward F. McClay, Kristi McIntyre, Tarek Mekhail, A. Misino, Olivier Molinier, Alessandro Morabito, Éva Morócz, Veronika Müller, Tünde Nagy, Anthony V. Nguyen, Emmanuel A. Nidhiry, Ian J. Okazaki, A.L. Ortega Granados, Gyula Ostoros, D. Oubre, Scott Owen, Krishna Pachipala, David Park, Pareshkumar Patel, Ivor Percent, M. Pérol, Solange Peters, Berber Piet, David Planchard, Andreas Polychronis, Santiago Ponce Aix, Elvire Pons‐Tostivint, Sanjaykumar Popat, Mariano Provencio, Xavier Quantin, Gilles Quéré, Noman M. Rafique, Ryan Ramaekers, Martin Reck, Tony Reiman, Niels Reinmuth, Craig H. Reynolds, Delvys Rodríguez‐Abreu, Gianpiero Romano, Tammy Roque, Matthew Salzberg, Rachel E. Sanborn, Sergio Sandiego, Eric Schaefer, Marshall T. Schreeder, Nagashree Seetharamu, Lasika Seneviratne, Purvi Shah, Leonid Shunyakov, Dennis Slater, Héctor Soto Parrà, Johannes Stigt, Joseph Stilwill, Jingdong Su, Veerle Surmont, Alicia Swink, Zsuzsanna Szalai, Toby Talbot, Álvaro Taus Garcia, Willemijn S.M.E. Theelen, Jonathan R. Thompson, Marcello Tiseo, Dipesh Uprety, James Uyeki, Kornelius Cor van der Leest, Anthony Van Ho, John van Putten, Sergio Vázquez‐Estévez, Andrea Veatch, A. Vergnenègre, Patrick J. Ward, Amy Weise, Matthias Weiß, Matthew Whitehurst, Silvia Zai, Gérard Zalcman, Richard Zuniga,
Tópico(s)Pancreatic and Hepatic Oncology Research
Resumo•Phase III trial of sitra + nivo compared with docetaxel in patients with advanced nonsquamous NSCLC. •The study evaluated whether CPI resistance can be overcome in patients treated with platinum-based chemotherapy and CPI. •The primary endpoint of improved OS with sitra + nivo versus docetaxel was not met. •The safety profiles of both regimens were consistent with previous reports, with no new safety signals. Background Checkpoint inhibitor (CPI) therapy revolutionized treatment for advanced non-small-cell lung cancer (NSCLC); however, most patients progress due to primary or acquired resistance. Sitravatinib is a receptor tyrosine kinase inhibitor that can shift the immunosuppressive tumor microenvironment toward an immunostimulatory state. Combining sitravatinib with nivolumab (sitra + nivo) may potentially overcome initial CPI resistance. Patients and methods In the phase III SAPPHIRE study, patients with advanced non-oncogenic driven, nonsquamous NSCLC who initially benefited from (≥4 months on CPI without progression) and subsequently experienced disease progression on or after CPI combined with or following platinum-based chemotherapy were randomized 1 : 1 to sitra (100 mg once daily administered orally) + nivo (240 mg every 2 weeks or 480 mg every 4 weeks administered intravenously) or docetaxel (75 mg/m2 every 3 weeks administered intravenously). The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR; all assessed by blinded independent central review), and safety. Results A total of 577 patients included randomized: sitra + nivo, n = 284; docetaxel, n = 293 (median follow-up, 17.1 months). Sitra + nivo did not significantly improve OS versus docetaxel [median, 12.2 versus 10.6 months; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.70-1.05; P = 0.144]. The median PFS was 4.4 versus 5.4 months, respectively (HR 1.08, 95% CI 0.89-1.32; P = 0.452). The ORR was 15.6% for sitra + nivo and 17.2% for docetaxel (P = 0.597); CBR was 75.5% and 64.5%, respectively (P = 0.004); median DOR was 7.4 versus 7.1 months, respectively (P = 0.924). Grade ≥3 treatment-related adverse events were observed in 53.0% versus 66.7% of patients receiving sitra + nivo versus docetaxel, respectively. Conclusions Although median OS was numerically longer with sitra + nivo, the primary endpoint was not met in patients with previously treated advanced nonsquamous NSCLC. The safety profiles demonstrated were consistent with previous reports. Checkpoint inhibitor (CPI) therapy revolutionized treatment for advanced non-small-cell lung cancer (NSCLC); however, most patients progress due to primary or acquired resistance. Sitravatinib is a receptor tyrosine kinase inhibitor that can shift the immunosuppressive tumor microenvironment toward an immunostimulatory state. Combining sitravatinib with nivolumab (sitra + nivo) may potentially overcome initial CPI resistance. In the phase III SAPPHIRE study, patients with advanced non-oncogenic driven, nonsquamous NSCLC who initially benefited from (≥4 months on CPI without progression) and subsequently experienced disease progression on or after CPI combined with or following platinum-based chemotherapy were randomized 1 : 1 to sitra (100 mg once daily administered orally) + nivo (240 mg every 2 weeks or 480 mg every 4 weeks administered intravenously) or docetaxel (75 mg/m2 every 3 weeks administered intravenously). The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR; all assessed by blinded independent central review), and safety. A total of 577 patients included randomized: sitra + nivo, n = 284; docetaxel, n = 293 (median follow-up, 17.1 months). Sitra + nivo did not significantly improve OS versus docetaxel [median, 12.2 versus 10.6 months; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.70-1.05; P = 0.144]. The median PFS was 4.4 versus 5.4 months, respectively (HR 1.08, 95% CI 0.89-1.32; P = 0.452). The ORR was 15.6% for sitra + nivo and 17.2% for docetaxel (P = 0.597); CBR was 75.5% and 64.5%, respectively (P = 0.004); median DOR was 7.4 versus 7.1 months, respectively (P = 0.924). Grade ≥3 treatment-related adverse events were observed in 53.0% versus 66.7% of patients receiving sitra + nivo versus docetaxel, respectively. Although median OS was numerically longer with sitra + nivo, the primary endpoint was not met in patients with previously treated advanced nonsquamous NSCLC. The safety profiles demonstrated were consistent with previous reports.
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