Tivozanib plus nivolumab versus tivozanib monotherapy in patients with renal cell carcinoma following an immune checkpoint inhibitor: results of the phase 3 TiNivo-2 Study.
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| Title: | Tivozanib plus nivolumab versus tivozanib monotherapy in patients with renal cell carcinoma following an immune checkpoint inhibitor: results of the phase 3 TiNivo-2 Study. |
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| Authors: | Choueiri, Toni K (AUTHOR), Albiges, Laurence (AUTHOR), Barthélémy, Philippe (AUTHOR), Iacovelli, Roberto (AUTHOR), Emambux, Sheik (AUTHOR), Molina-Cerrillo, Javier (AUTHOR), Garmezy, Benjamin (AUTHOR), Barata, Pedro (AUTHOR), Basu, Arnab (AUTHOR), Bourlon, Maria T (AUTHOR), Moon, Helen (AUTHOR), Ratta, Raffaele (AUTHOR), McKay, Rana R (AUTHOR), Chehrazi-Raffle, Alexander (AUTHOR), Hammers, Hans (AUTHOR), Heng, Daniel Y C (AUTHOR), Braendle, Edgar (AUTHOR), Beckermann, Kathryn E (AUTHOR), McGregor, Bradley A (AUTHOR), Motzer, Robert J (AUTHOR) |
| Source: | Lancet. Oct2024, Vol. 404 Issue 10460, p1309-1320. 12p. |
| Subjects: | Vascular endothelial growth factor receptors, Immune checkpoint inhibitors, Clinical trials, Protein-tyrosine kinase inhibitors, Renal cell carcinoma, Progression-free survival |
| Abstract: | Immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor receptor tyrosine kinase inhibitors are cornerstones of first-line treatment for advanced renal cell carcinoma; however, optimal treatment sequencing after progression is unknown. This study aimed to assess clinical outcomes of tivozanib–nivolumab versus tivozanib monotherapy in patients with metastatic renal cell carcinoma who have progressed following one or two lines of therapy in the post-ICI setting. TiNivo-2 is a multicentre, randomised, open-label, phase 3 trial at 190 sites across 16 countries, in Australia, Europe, North America, and South America. Patients with advanced renal cell carcinoma and progression during or after one to two previous lines of therapy (including one ICI) were randomised 1:1 to tivozanib (0·89 mg per day, orally) plus nivolumab (480 mg every 4 weeks, intravenously) or tivozanib (1·34 mg per day, orally). Randomisation was stratified by immediate previous therapy (ICI or non-ICI) and International Metastatic Renal Cell Carcinoma Database Consortium risk category. The primary endpoint was progression-free survival (PFS), defined as the time from randomisation to first documentation of objective progressive disease according to RECIST 1·1 or death from any cause, whichever came first, by independent radiology review. Efficacy was evaluated in the intention-to-treat population, and safety was assessed in patients who received one or more doses of the study drug. This trial was registered on ClinicalTrials.gov (NCT04987203) and is active and not recruiting. From Nov 4, 2021, to June 16, 2023, 343 patients were randomly assigned to tivozanib–nivolumab (n=171) or tivozanib monotherapy (n=172). Median follow-up was 12·0 months. Median PFS was 5·7 months (95% CI 4·0–7·4) with tivozanib–nivolumab and 7·4 months (5·6–9·2) with tivozanib monotherapy (hazard ratio 1·10, 95% CI 0·84–1·43; p=0·49). Among those with an ICI as their immediate previous therapy (n=244), median PFS was 7·4 months (95% CI 5·6–9·6) with tivozanib–nivolumab and 9·2 months (7·4–10·0) with tivozanib monotherapy. With non-ICIs as the most recent therapy, lower median PFS was observed, with no difference between groups (tivozanib–nivolumab 3·7 months [95% CI 2·7–5·4] and with tivozanib monotherapy 3·7 months [1·9–7·2]). Serious adverse events occurred in 54 (32%) of 168 patients receiving tivozanib–nivolumab and 64 (37%) of 171 patients receiving tivozanib monotherapy. One (<1%) treatment-related death occurred (tivozanib group). These data further support that ICI rechallenge should be discouraged in patients with advanced renal cell carcinoma. Furthermore, these data suggest that tivozanib monotherapy has efficacy in the post-ICI setting. Aveo Pharmaceuticals. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 180092805 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Tivozanib plus nivolumab versus tivozanib monotherapy in patients with renal cell carcinoma following an immune checkpoint inhibitor: results of the phase 3 TiNivo-2 Study. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Choueiri%2C+Toni+K%22">Choueiri, Toni K</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Albiges%2C+Laurence%22">Albiges, Laurence</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Barthélémy%2C+Philippe%22">Barthélémy, Philippe</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Iacovelli%2C+Roberto%22">Iacovelli, Roberto</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Emambux%2C+Sheik%22">Emambux, Sheik</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Molina-Cerrillo%2C+Javier%22">Molina-Cerrillo, Javier</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Garmezy%2C+Benjamin%22">Garmezy, Benjamin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Barata%2C+Pedro%22">Barata, Pedro</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Basu%2C+Arnab%22">Basu, Arnab</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bourlon%2C+Maria+T%22">Bourlon, Maria T</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Moon%2C+Helen%22">Moon, Helen</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ratta%2C+Raffaele%22">Ratta, Raffaele</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22McKay%2C+Rana+R%22">McKay, Rana R</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chehrazi-Raffle%2C+Alexander%22">Chehrazi-Raffle, Alexander</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hammers%2C+Hans%22">Hammers, Hans</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Heng%2C+Daniel+Y+C%22">Heng, Daniel Y C</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Braendle%2C+Edgar%22">Braendle, Edgar</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Beckermann%2C+Kathryn+E%22">Beckermann, Kathryn E</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22McGregor%2C+Bradley+A%22">McGregor, Bradley A</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Motzer%2C+Robert+J%22">Motzer, Robert J</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Lancet%22">Lancet</searchLink>. Oct2024, Vol. 404 Issue 10460, p1309-1320. 12p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Vascular+endothelial+growth+factor+receptors%22">Vascular endothelial growth factor receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Immune+checkpoint+inhibitors%22">Immune checkpoint inhibitors</searchLink><br /><searchLink fieldCode="DE" term="%22Clinical+trials%22">Clinical trials</searchLink><br /><searchLink fieldCode="DE" term="%22Protein-tyrosine+kinase+inhibitors%22">Protein-tyrosine kinase inhibitors</searchLink><br /><searchLink fieldCode="DE" term="%22Renal+cell+carcinoma%22">Renal cell carcinoma</searchLink><br /><searchLink fieldCode="DE" term="%22Progression-free+survival%22">Progression-free survival</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor receptor tyrosine kinase inhibitors are cornerstones of first-line treatment for advanced renal cell carcinoma; however, optimal treatment sequencing after progression is unknown. This study aimed to assess clinical outcomes of tivozanib–nivolumab versus tivozanib monotherapy in patients with metastatic renal cell carcinoma who have progressed following one or two lines of therapy in the post-ICI setting. TiNivo-2 is a multicentre, randomised, open-label, phase 3 trial at 190 sites across 16 countries, in Australia, Europe, North America, and South America. Patients with advanced renal cell carcinoma and progression during or after one to two previous lines of therapy (including one ICI) were randomised 1:1 to tivozanib (0·89 mg per day, orally) plus nivolumab (480 mg every 4 weeks, intravenously) or tivozanib (1·34 mg per day, orally). Randomisation was stratified by immediate previous therapy (ICI or non-ICI) and International Metastatic Renal Cell Carcinoma Database Consortium risk category. The primary endpoint was progression-free survival (PFS), defined as the time from randomisation to first documentation of objective progressive disease according to RECIST 1·1 or death from any cause, whichever came first, by independent radiology review. Efficacy was evaluated in the intention-to-treat population, and safety was assessed in patients who received one or more doses of the study drug. This trial was registered on ClinicalTrials.gov (NCT04987203) and is active and not recruiting. From Nov 4, 2021, to June 16, 2023, 343 patients were randomly assigned to tivozanib–nivolumab (n=171) or tivozanib monotherapy (n=172). Median follow-up was 12·0 months. Median PFS was 5·7 months (95% CI 4·0–7·4) with tivozanib–nivolumab and 7·4 months (5·6–9·2) with tivozanib monotherapy (hazard ratio 1·10, 95% CI 0·84–1·43; p=0·49). Among those with an ICI as their immediate previous therapy (n=244), median PFS was 7·4 months (95% CI 5·6–9·6) with tivozanib–nivolumab and 9·2 months (7·4–10·0) with tivozanib monotherapy. With non-ICIs as the most recent therapy, lower median PFS was observed, with no difference between groups (tivozanib–nivolumab 3·7 months [95% CI 2·7–5·4] and with tivozanib monotherapy 3·7 months [1·9–7·2]). Serious adverse events occurred in 54 (32%) of 168 patients receiving tivozanib–nivolumab and 64 (37%) of 171 patients receiving tivozanib monotherapy. One (<1%) treatment-related death occurred (tivozanib group). These data further support that ICI rechallenge should be discouraged in patients with advanced renal cell carcinoma. Furthermore, these data suggest that tivozanib monotherapy has efficacy in the post-ICI setting. Aveo Pharmaceuticals. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/S0140-6736(24)01758-6 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 12 StartPage: 1309 Subjects: – SubjectFull: Vascular endothelial growth factor receptors Type: general – SubjectFull: Immune checkpoint inhibitors Type: general – SubjectFull: Clinical trials Type: general – SubjectFull: Protein-tyrosine kinase inhibitors Type: general – SubjectFull: Renal cell carcinoma Type: general – SubjectFull: Progression-free survival Type: general Titles: – TitleFull: Tivozanib plus nivolumab versus tivozanib monotherapy in patients with renal cell carcinoma following an immune checkpoint inhibitor: results of the phase 3 TiNivo-2 Study. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Choueiri, Toni K – PersonEntity: Name: NameFull: Albiges, Laurence – PersonEntity: Name: NameFull: Barthélémy, Philippe – PersonEntity: Name: NameFull: Iacovelli, Roberto – PersonEntity: Name: NameFull: Emambux, Sheik – PersonEntity: Name: NameFull: Molina-Cerrillo, Javier – PersonEntity: Name: NameFull: Garmezy, Benjamin – PersonEntity: Name: NameFull: Barata, Pedro – PersonEntity: Name: NameFull: Basu, Arnab – PersonEntity: Name: NameFull: Bourlon, Maria T – PersonEntity: Name: NameFull: Moon, Helen – PersonEntity: Name: NameFull: Ratta, Raffaele – PersonEntity: Name: NameFull: McKay, Rana R – PersonEntity: Name: NameFull: Chehrazi-Raffle, Alexander – PersonEntity: Name: NameFull: Hammers, Hans – PersonEntity: Name: NameFull: Heng, Daniel Y C – PersonEntity: Name: NameFull: Braendle, Edgar – PersonEntity: Name: NameFull: Beckermann, Kathryn E – PersonEntity: Name: NameFull: McGregor, Bradley A – PersonEntity: Name: NameFull: Motzer, Robert J IsPartOfRelationships: – BibEntity: Dates: – D: 05 M: 10 Text: Oct2024 Type: published Y: 2024 Identifiers: – Type: issn-print Value: 01406736 Numbering: – Type: volume Value: 404 – Type: issue Value: 10460 Titles: – TitleFull: Lancet Type: main |
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