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
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...
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| Veröffentlicht in: | The Lancet (British edition) 2024-10, Vol.404 (10460), p.1309-1320 |
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| creator | Choueiri, Toni K Albiges, Laurence Barthélémy, Philippe Iacovelli, Roberto Emambux, Sheik Molina-Cerrillo, Javier Garmezy, Benjamin Barata, Pedro Basu, Arnab Bourlon, Maria T Moon, Helen Ratta, Raffaele McKay, Rana R Chehrazi-Raffle, Alexander Hammers, Hans Heng, Daniel Y C Braendle, Edgar Beckermann, Kathryn E McGregor, Bradley A Motzer, Robert J |
| description | 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 ( |
| doi_str_mv | 10.1016/S0140-6736(24)01758-6 |
| format | Article |
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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.</description><identifier>ISSN: 0140-6736</identifier><identifier>ISSN: 1474-547X</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(24)01758-6</identifier><identifier>PMID: 39284329</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Carcinoma, Renal Cell - drug therapy ; Cell death ; Combination therapy ; Drug dosages ; Effectiveness ; FDA approval ; Female ; Growth factors ; Health services ; Humans ; Hypertension ; Immune checkpoint inhibitors ; Immune Checkpoint Inhibitors - administration & dosage ; Immune Checkpoint Inhibitors - adverse effects ; Immune Checkpoint Inhibitors - therapeutic use ; Immunotherapy ; Inhibitors ; Kidney cancer ; Kidney Neoplasms - drug therapy ; Kidney Neoplasms - pathology ; Kinases ; Ligands ; Male ; Metastases ; Metastasis ; Middle Aged ; Monoclonal antibodies ; Nivolumab - administration & dosage ; Nivolumab - adverse effects ; Nivolumab - therapeutic use ; Oncology ; Patients ; Phenylurea Compounds - administration & dosage ; Phenylurea Compounds - adverse effects ; Phenylurea Compounds - therapeutic use ; Population studies ; Progression-Free Survival ; Protein-tyrosine kinase receptors ; Quinolines - administration & dosage ; Quinolines - therapeutic use ; Radiology ; Randomization ; Renal cell carcinoma ; Targeted cancer therapy ; Therapy ; Tyrosine ; Vascular endothelial growth factor</subject><ispartof>The Lancet (British edition), 2024-10, Vol.404 (10460), p.1309-1320</ispartof><rights>2024 Elsevier Ltd</rights><rights>Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.</rights><rights>2024. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1869-e0179a9f732d26cee6d21026e3ab88d7c0e61abe39c1dc61c5b4380f4eb35fe93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0140-6736(24)01758-6$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39284329$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Choueiri, Toni K</creatorcontrib><creatorcontrib>Albiges, Laurence</creatorcontrib><creatorcontrib>Barthélémy, Philippe</creatorcontrib><creatorcontrib>Iacovelli, Roberto</creatorcontrib><creatorcontrib>Emambux, Sheik</creatorcontrib><creatorcontrib>Molina-Cerrillo, Javier</creatorcontrib><creatorcontrib>Garmezy, Benjamin</creatorcontrib><creatorcontrib>Barata, Pedro</creatorcontrib><creatorcontrib>Basu, Arnab</creatorcontrib><creatorcontrib>Bourlon, Maria T</creatorcontrib><creatorcontrib>Moon, Helen</creatorcontrib><creatorcontrib>Ratta, Raffaele</creatorcontrib><creatorcontrib>McKay, Rana R</creatorcontrib><creatorcontrib>Chehrazi-Raffle, Alexander</creatorcontrib><creatorcontrib>Hammers, Hans</creatorcontrib><creatorcontrib>Heng, Daniel Y C</creatorcontrib><creatorcontrib>Braendle, Edgar</creatorcontrib><creatorcontrib>Beckermann, Kathryn E</creatorcontrib><creatorcontrib>McGregor, Bradley A</creatorcontrib><creatorcontrib>Motzer, Robert J</creatorcontrib><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</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>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.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Carcinoma, Renal Cell - drug therapy</subject><subject>Cell death</subject><subject>Combination therapy</subject><subject>Drug dosages</subject><subject>Effectiveness</subject><subject>FDA approval</subject><subject>Female</subject><subject>Growth factors</subject><subject>Health services</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Immune checkpoint inhibitors</subject><subject>Immune Checkpoint Inhibitors - administration & dosage</subject><subject>Immune Checkpoint Inhibitors - adverse effects</subject><subject>Immune Checkpoint Inhibitors - therapeutic use</subject><subject>Immunotherapy</subject><subject>Inhibitors</subject><subject>Kidney cancer</subject><subject>Kidney Neoplasms - drug therapy</subject><subject>Kidney Neoplasms - pathology</subject><subject>Kinases</subject><subject>Ligands</subject><subject>Male</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Nivolumab - 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Academic</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choueiri, Toni K</au><au>Albiges, Laurence</au><au>Barthélémy, Philippe</au><au>Iacovelli, Roberto</au><au>Emambux, Sheik</au><au>Molina-Cerrillo, Javier</au><au>Garmezy, Benjamin</au><au>Barata, Pedro</au><au>Basu, Arnab</au><au>Bourlon, Maria T</au><au>Moon, Helen</au><au>Ratta, Raffaele</au><au>McKay, Rana R</au><au>Chehrazi-Raffle, Alexander</au><au>Hammers, Hans</au><au>Heng, Daniel Y C</au><au>Braendle, Edgar</au><au>Beckermann, Kathryn E</au><au>McGregor, Bradley A</au><au>Motzer, Robert J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2024-10-05</date><risdate>2024</risdate><volume>404</volume><issue>10460</issue><spage>1309</spage><epage>1320</epage><pages>1309-1320</pages><issn>0140-6736</issn><issn>1474-547X</issn><eissn>1474-547X</eissn><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><cop>England</cop><pub>Elsevier Ltd</pub><pmid>39284329</pmid><doi>10.1016/S0140-6736(24)01758-6</doi><tpages>12</tpages></addata></record> |
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| identifier | ISSN: 0140-6736 |
| ispartof | The Lancet (British edition), 2024-10, Vol.404 (10460), p.1309-1320 |
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| subjects | Adult Aged Antineoplastic Combined Chemotherapy Protocols - therapeutic use Carcinoma, Renal Cell - drug therapy Cell death Combination therapy Drug dosages Effectiveness FDA approval Female Growth factors Health services Humans Hypertension Immune checkpoint inhibitors Immune Checkpoint Inhibitors - administration & dosage Immune Checkpoint Inhibitors - adverse effects Immune Checkpoint Inhibitors - therapeutic use Immunotherapy Inhibitors Kidney cancer Kidney Neoplasms - drug therapy Kidney Neoplasms - pathology Kinases Ligands Male Metastases Metastasis Middle Aged Monoclonal antibodies Nivolumab - administration & dosage Nivolumab - adverse effects Nivolumab - therapeutic use Oncology Patients Phenylurea Compounds - administration & dosage Phenylurea Compounds - adverse effects Phenylurea Compounds - therapeutic use Population studies Progression-Free Survival Protein-tyrosine kinase receptors Quinolines - administration & dosage Quinolines - therapeutic use Radiology Randomization Renal cell carcinoma Targeted cancer therapy Therapy Tyrosine Vascular endothelial growth factor |
| 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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