Titre
SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Borghaei, H.
Auteure/Auteur
de Marinis, F.
Auteure/Auteur
Dumoulin, D.
Auteure/Auteur
Reynolds, C.
Auteure/Auteur
Theelen, WSME
Auteure/Auteur
Percent, I.
Auteure/Auteur
Gutierrez Calderon, V.
Auteure/Auteur
Johnson, M.L.
Auteure/Auteur
Madroszyk-Flandin, A.
Auteure/Auteur
Garon, E.B.
Auteure/Auteur
He, K.
Auteure/Auteur
Planchard, D.
Auteure/Auteur
Reck, M.
Auteure/Auteur
Popat, S.
Auteure/Auteur
Herbst, R.S.
Auteure/Auteur
Leal, T.A.
Auteure/Auteur
Shazer, R.L.
Auteure/Auteur
Yan, X.
Auteure/Auteur
Harrigan, R.
Auteure/Auteur
Peters, S.
Auteure/Auteur
Contributrices/contributeurs
Abdel-Karim, I.
Abdelsalam, M.
Addeo, A.
Aguado, C.
Alexander, P.
Alt, J.
Azzi, G.
Balaraman, R.
Biesma, B.
Blackhall, F.
Bohnet, S.
Boleti, E.
Borghaei, H.
Bradbury, P.
Brighenti, M.
Campbell, N.
Campbell, T.
Canon, J.L.
Cappuzzo, F.
Costa, E.C.
Cavanna, L.
Cetnar, J.
Chella, A.
Chouaid, C.
Christoph, D.
Castán, J.C.
Dakhil, S.
de Castro Carpeño, F.J.
de Marinis, F.
Delmonte, A.
Demedts, I.
Demey, W.
Dits, J.
Del Pilar Diz Taín, M.
Gómez, M.D.
Dorius, T.
Dumoulin, D.
Duruisseaux, M.
Eaton, K.
González, E.E.
Evans, D.
Faehling, M.
Farrell, N.
Feinstein, T.
Font, E.F.
Garcia Campelo, M.R.
Garon, E.
Garrido López, M.P.
Germonpré, P.
Gersten, T.
Cao, M.G.
Gopaluni, S.
Greillier, L.
Grossi, F.
Guisier, F.
Gurubhagavatula, S.
Calderón, V.G.
Hakimian, D.
Hall, R.
Hao, D.
Harris, R.
Hashemi, S.
He, K.
Hendriks, L.
Huang, C.
Ibrahim, E.
Jain, S.
Johnson, M.
Jones, B.
Jones, M.
Juan Vidal, Ó.J.
Juergens, R.
Kaderbhai, C.
Kastelijn, EAL
Keresztes, R.
Kio, E.
Kokowski, K.
Konduri, K.
Kulkarni, S.
Kuon, J.
Kurkjian, C.
Labbé, C.
Lerner, R.
Lim, F.
Madroszyk-Flandin, A.
Marathe, O.
Martincic, D.
McClay, E.
McIntyre, K.
Mekhail, T.
Misino, A.
Molinier, O.
Morabito, A.
Morócz, É.
Müller, V.
Nagy, T.
Nguyen, A.V.
Nidhiry, E.
Okazaki, I.
Ortega-Granados, A.L.
Ostoros, G.
Oubre, D.
Owen, S.
Pachipala, K.
Park, D.
Patel, P.
Percent, I.
Pérol, M.
Peters, S.
Piet, B.
Planchard, D.
Polychronis, A.
Aix, S.P.
Pons-Tostivint, E.
Popat, S.
Pulla, M.P.
Quantin, X.
Quéré, G.
Rafique, N.
Ramaekers, R.
Reck, M.
Reiman, A.
Reinmuth, N.
Reynolds, C.
Rodríguez-Abreu, D.
Romano, G.
Roque, T.
Salzberg, M.
Sanborn, R.
Sandiego, S.
Schaefer, E.
Schreeder, M.
Seetharamu, N.
Seneviratne, L.
Shah, P.
Shunyakov, L.
Slater, D.
Parra, H.S.
Stigt, J.
Stilwill, J.
Su, J.
Surmont, V.
Swink, A.
Szalai, Z.
Talbot, T.
Garcia, A.T.
Theelen, W.
Thompson, J.
Tiseo, M.
Uprety, D.
Uyeki, J.
van der Leest, K.C.
Van Ho, A.
van Putten, J.
Estévez, S.V.
Veatch, A.
Vergnenègre, A.
Ward, P.
Weise, A.
Weiss, M.
Whitehurst, M.
Zai, S.
Zalcman, G.
Zuniga, R.
Groupes de travail
SAPPHIRE Investigators
Liens vers les personnes
Liens vers les unités
ISSN
1569-8041
Statut éditorial
Publié
Date de publication
2024-01
Volume
35
Numéro
1
Première page
66
Dernière page/numéro d’article
76
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Randomized Controlled Trial ; Clinical Trial, Phase III ; Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
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/m <sup>2</sup> 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.
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/m <sup>2</sup> 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.
PID Serval
serval:BIB_1ED7B5418D24
PMID
Date de création
2023-10-26T13:27:00.628Z
Date de création dans IRIS
2025-05-20T15:20:37Z