SAPPHIRE : phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Copyright © 2023. Published by Elsevier Ltd..
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:35 |
---|---|
Enthalten in: |
Annals of oncology : official journal of the European Society for Medical Oncology - 35(2024), 1 vom: 15. Jan., Seite 66-76 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Borghaei, H [VerfasserIn] |
---|
Links: |
---|
Themen: |
15H5577CQD |
---|
Anmerkungen: |
Date Completed 15.01.2024 Date Revised 15.01.2024 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1016/j.annonc.2023.10.004 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM363591397 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM363591397 | ||
003 | DE-627 | ||
005 | 20240115231901.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.annonc.2023.10.004 |2 doi | |
028 | 5 | 2 | |a pubmed24n1260.xml |
035 | |a (DE-627)NLM363591397 | ||
035 | |a (NLM)37866811 | ||
035 | |a (PII)S0923-7534(23)04019-X | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Borghaei, H |e verfasserin |4 aut | |
245 | 1 | 0 | |a SAPPHIRE |b phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 15.01.2024 | ||
500 | |a Date Revised 15.01.2024 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2023. Published by Elsevier Ltd. | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
650 | 4 | |a Randomized Controlled Trial | |
650 | 4 | |a Clinical Trial, Phase III | |
650 | 4 | |a Journal Article | |
650 | 4 | |a NSCLC | |
650 | 4 | |a nivolumab | |
650 | 4 | |a sitravatinib | |
650 | 7 | |a Docetaxel |2 NLM | |
650 | 7 | |a 15H5577CQD |2 NLM | |
650 | 7 | |a Nivolumab |2 NLM | |
650 | 7 | |a 31YO63LBSN |2 NLM | |
650 | 7 | |a sitravatinib |2 NLM | |
650 | 7 | |a CWG62Q1VTB |2 NLM | |
650 | 7 | |a Anilides |2 NLM | |
650 | 7 | |a Pyridines |2 NLM | |
700 | 1 | |a de Marinis, F |e verfasserin |4 aut | |
700 | 1 | |a Dumoulin, D |e verfasserin |4 aut | |
700 | 1 | |a Reynolds, C |e verfasserin |4 aut | |
700 | 1 | |a Theelen, W S M E |e verfasserin |4 aut | |
700 | 1 | |a Percent, I |e verfasserin |4 aut | |
700 | 1 | |a Gutierrez Calderon, V |e verfasserin |4 aut | |
700 | 1 | |a Johnson, M L |e verfasserin |4 aut | |
700 | 1 | |a Madroszyk-Flandin, A |e verfasserin |4 aut | |
700 | 1 | |a Garon, E B |e verfasserin |4 aut | |
700 | 1 | |a He, K |e verfasserin |4 aut | |
700 | 1 | |a Planchard, D |e verfasserin |4 aut | |
700 | 1 | |a Reck, M |e verfasserin |4 aut | |
700 | 1 | |a Popat, S |e verfasserin |4 aut | |
700 | 1 | |a Herbst, R S |e verfasserin |4 aut | |
700 | 1 | |a Leal, T A |e verfasserin |4 aut | |
700 | 1 | |a Shazer, R L |e verfasserin |4 aut | |
700 | 1 | |a Yan, X |e verfasserin |4 aut | |
700 | 1 | |a Harrigan, R |e verfasserin |4 aut | |
700 | 1 | |a Peters, S |e verfasserin |4 aut | |
700 | 0 | |a SAPPHIRE Investigators |e verfasserin |4 aut | |
700 | 1 | |a Abdel-Karim, Isam |e investigator |4 oth | |
700 | 1 | |a Abdelsalam, Mahmoud |e investigator |4 oth | |
700 | 1 | |a Addeo, Alfredo |e investigator |4 oth | |
700 | 1 | |a Aguado, Carlos |e investigator |4 oth | |
700 | 1 | |a Alexander, Patrick |e investigator |4 oth | |
700 | 1 | |a Alt, Jürgen |e investigator |4 oth | |
700 | 1 | |a Azzi, Georges |e investigator |4 oth | |
700 | 1 | |a Balaraman, Rama |e investigator |4 oth | |
700 | 1 | |a Biesma, Bonne |e investigator |4 oth | |
700 | 1 | |a Blackhall, Fiona |e investigator |4 oth | |
700 | 1 | |a Bohnet, Sabine |e investigator |4 oth | |
700 | 1 | |a Boleti, Ekaterini |e investigator |4 oth | |
700 | 1 | |a Borghaei, Hossein |e investigator |4 oth | |
700 | 1 | |a Bradbury, Penelope |e investigator |4 oth | |
700 | 1 | |a Brighenti, Matteo |e investigator |4 oth | |
700 | 1 | |a Campbell, Nicholas |e investigator |4 oth | |
700 | 1 | |a Campbell, Toby |e investigator |4 oth | |
700 | 1 | |a Canon, Jean-Luc |e investigator |4 oth | |
700 | 1 | |a Cappuzzo, Federico |e investigator |4 oth | |
700 | 1 | |a Costa, Enric Carcereny |e investigator |4 oth | |
700 | 1 | |a Cavanna, Luigi |e investigator |4 oth | |
700 | 1 | |a Cetnar, Jeremy |e investigator |4 oth | |
700 | 1 | |a Chella, Antonio |e investigator |4 oth | |
700 | 1 | |a Chouaid, Christos |e investigator |4 oth | |
700 | 1 | |a Christoph, Daniel |e investigator |4 oth | |
700 | 1 | |a Castán, Javier Cortés |e investigator |4 oth | |
700 | 1 | |a Dakhil, Shaker |e investigator |4 oth | |
700 | 1 | |a de Castro Carpeño, Francisco Javier |e investigator |4 oth | |
700 | 1 | |a de Marinis, Filippo |e investigator |4 oth | |
700 | 1 | |a Delmonte, Angelo |e investigator |4 oth | |
700 | 1 | |a Demedts, Ingel |e investigator |4 oth | |
700 | 1 | |a Demey, Wim |e investigator |4 oth | |
700 | 1 | |a Dits, Joyce |e investigator |4 oth | |
700 | 1 | |a Del Pilar Diz Taín, Maria |e investigator |4 oth | |
700 | 1 | |a Gómez, Manuel Dómine |e investigator |4 oth | |
700 | 1 | |a Dorius, Timothy |e investigator |4 oth | |
700 | 1 | |a Dumoulin, Daphne |e investigator |4 oth | |
700 | 1 | |a Duruisseaux, Michaël |e investigator |4 oth | |
700 | 1 | |a Eaton, Keith |e investigator |4 oth | |
700 | 1 | |a González, Emilio Esteban |e investigator |4 oth | |
700 | 1 | |a Evans, Devon |e investigator |4 oth | |
700 | 1 | |a Faehling, Martin |e investigator |4 oth | |
700 | 1 | |a Farrell, Nicholas |e investigator |4 oth | |
700 | 1 | |a Feinstein, Trevor |e investigator |4 oth | |
700 | 1 | |a Font, Enriqueta Felip |e investigator |4 oth | |
700 | 1 | |a Garcia Campelo, Maria Rosario |e investigator |4 oth | |
700 | 1 | |a Garon, Edward |e investigator |4 oth | |
700 | 1 | |a Garrido López, María Pilar |e investigator |4 oth | |
700 | 1 | |a Germonpré, Paul |e investigator |4 oth | |
700 | 1 | |a Gersten, Todd |e investigator |4 oth | |
700 | 1 | |a Cao, Maria Gonzalez |e investigator |4 oth | |
700 | 1 | |a Gopaluni, Srivalli |e investigator |4 oth | |
700 | 1 | |a Greillier, Laurent |e investigator |4 oth | |
700 | 1 | |a Grossi, Francesco |e investigator |4 oth | |
700 | 1 | |a Guisier, Florian |e investigator |4 oth | |
700 | 1 | |a Gurubhagavatula, Sarada |e investigator |4 oth | |
700 | 1 | |a Calderón, Vanesa Gutiérrez |e investigator |4 oth | |
700 | 1 | |a Hakimian, David |e investigator |4 oth | |
700 | 1 | |a Hall, Richard |c Jr |e investigator |4 oth | |
700 | 1 | |a Hao, Desirée |e investigator |4 oth | |
700 | 1 | |a Harris, Ronald |e investigator |4 oth | |
700 | 1 | |a Hashemi, Sayed |e investigator |4 oth | |
700 | 1 | |a He, Kai |e investigator |4 oth | |
700 | 1 | |a Hendriks, Lizza |e investigator |4 oth | |
700 | 1 | |a Huang, Chao |e investigator |4 oth | |
700 | 1 | |a Ibrahim, Emad |e investigator |4 oth | |
700 | 1 | |a Jain, Sharad |e investigator |4 oth | |
700 | 1 | |a Johnson, Melissa |e investigator |4 oth | |
700 | 1 | |a Jones, Benjamin |e investigator |4 oth | |
700 | 1 | |a Jones, Monte |e investigator |4 oth | |
700 | 1 | |a Juan Vidal, Óscar José |e investigator |4 oth | |
700 | 1 | |a Juergens, Rosalyn |e investigator |4 oth | |
700 | 1 | |a Kaderbhai, Courèche |e investigator |4 oth | |
700 | 1 | |a Kastelijn, Elisabeth A Lisanne |e investigator |4 oth | |
700 | 1 | |a Keresztes, Roger |e investigator |4 oth | |
700 | 1 | |a Kio, Ebenezer |e investigator |4 oth | |
700 | 1 | |a Kokowski, Konrad |e investigator |4 oth | |
700 | 1 | |a Konduri, Kartik |e investigator |4 oth | |
700 | 1 | |a Kulkarni, Swati |e investigator |4 oth | |
700 | 1 | |a Kuon, Jonas |e investigator |4 oth | |
700 | 1 | |a Kurkjian, Carla |e investigator |4 oth | |
700 | 1 | |a Labbé, Catherine |e investigator |4 oth | |
700 | 1 | |a Lerner, Rachel |e investigator |4 oth | |
700 | 1 | |a Lim, Farah |e investigator |4 oth | |
700 | 1 | |a Madroszyk-Flandin, Anne |e investigator |4 oth | |
700 | 1 | |a Marathe, Omkar |e investigator |4 oth | |
700 | 1 | |a Martincic, Danko |e investigator |4 oth | |
700 | 1 | |a McClay, Edward |e investigator |4 oth | |
700 | 1 | |a McIntyre, Kristi |e investigator |4 oth | |
700 | 1 | |a Mekhail, Tarek |e investigator |4 oth | |
700 | 1 | |a Misino, Andrea |e investigator |4 oth | |
700 | 1 | |a Molinier, Olivier |e investigator |4 oth | |
700 | 1 | |a Morabito, Alessandro |e investigator |4 oth | |
700 | 1 | |a Morócz, Éva |e investigator |4 oth | |
700 | 1 | |a Müller, Veronika |e investigator |4 oth | |
700 | 1 | |a Nagy, Tünde |e investigator |4 oth | |
700 | 1 | |a Nguyen, Anthony V |e investigator |4 oth | |
700 | 1 | |a Nidhiry, Emmanuel |e investigator |4 oth | |
700 | 1 | |a Okazaki, Ian |e investigator |4 oth | |
700 | 1 | |a Ortega-Granados, Ana Laura |e investigator |4 oth | |
773 | 0 | 8 | |i Enthalten in |t Annals of oncology : official journal of the European Society for Medical Oncology |d 1990 |g 35(2024), 1 vom: 15. Jan., Seite 66-76 |w (DE-627)NLM012606308 |x 1569-8041 |7 nnns |
773 | 1 | 8 | |g volume:35 |g year:2024 |g number:1 |g day:15 |g month:01 |g pages:66-76 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.annonc.2023.10.004 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 35 |j 2024 |e 1 |b 15 |c 01 |h 66-76 |