SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer.
Details
Serval ID
serval:BIB_1ED7B5418D24
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer.
Journal
Annals of oncology
Working group(s)
SAPPHIRE Investigators
Contributor(s)
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.
ISSN
1569-8041 (Electronic)
ISSN-L
0923-7534
Publication state
Published
Issued date
01/2024
Peer-reviewed
Oui
Volume
35
Number
1
Pages
66-76
Language
english
Notes
Publication types: Randomized Controlled Trial ; Clinical Trial, Phase III ; Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
Keywords
Humans, Carcinoma, Non-Small-Cell Lung/pathology, Docetaxel/therapeutic use, Nivolumab/therapeutic use, Lung Neoplasms/pathology, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Tumor Microenvironment, Anilides, Pyridines, NSCLC, nivolumab, sitravatinib
Pubmed
Web of science
Create date
26/10/2023 15:27
Last modification date
12/03/2024 8:08
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