Ronan Flippot1, Cécile Dalban2, Brigitte Laguerre3, Delphine Borchiellini4, Gwénaelle Gravis5, Sylvie Négrier2, Christine Chevreau6, Florence Joly7, Lionnel Geoffrois8, Sylvain Ladoire9, Hakim Mahammedi10, Frédéric Rolland11, Marine Gross-Goupil12, Elise Deluche13, Frank Priou14, Mathieu Laramas15, Philippe Barthélémy16, Bérengère Narciso17, Nadine Houedé18, Stéphane Culine19, Stéphane Oudard20, Marina Chenot21, Florence Tantot22, Sylvie Chabaud2, Bernard Escudier1, Laurence Albiges1. 1. 1Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France. 2. 2Centre Léon Berard, Lyon, France. 3. 3Centre Eugene Marquis, Rennes, France. 4. 4Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France. 5. 5Institut Paoli Calmettes, Marseille, France. 6. 6Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France. 7. 7Centre François Baclesse, Caen, France. 8. 8Institut de Cancérologie de Lorraine, Vandoeuvre-lès-Nancy, France. 9. 9Centre Georges François Leclerc, Dijon, France. 10. 10Centre Jean Perrin, Clermont-Ferrand, France. 11. 11Centre René Gauducheau, Saint Herblain, France. 12. 12Bordeaux University Hospital, Bordeaux, France. 13. 13Limoges University Hospital, Limoges, France. 14. 14Centre Hospitalier de Vendée, La Roche sur Yon, France. 15. 15Alpes University Hospital, Grenoble, France. 16. 16Strasbourg University Hospital, Strasbourg, France. 17. 17Tours University Hospital, Tours, France. 18. 18Nimes University Hospital, Nimes, France. 19. 19Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, Paris, France. 20. 20Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France. 21. 21Université Montpellier, Montpellier, France. 22. 22GETUG Group, Unicancer, Paris, France.
Abstract
PURPOSE: Nivolumab is standard of care for patients with metastatic clear cell renal cell carcinoma (ccRCC) after failure of antiangiogenic therapies, but its activity on brain metastases from ccRCC remains unknown, because these patients were excluded from pivotal studies. We aimed to assess the activity of nivolumab in this population. METHODS: The GETUG-AFU 26 NIVOREN phase II trial assessed the activity and safety of nivolumab in patients with metastatic ccRCC who failed vascular endothelial growth factor-directed therapies (ClinicalTrials.gov identifier: NCT03013335). Patients with asymptomatic brain metastases were prospectively identified and underwent dedicated brain evaluation. Two cohorts were constituted: cohort A comprised patients with previously untreated brain metastases, and cohort B comprised patients whose brain metastases underwent prior therapy. The primary end point was intracranial response rate in cohort A. RESULTS: Seventy-three patients with brain metastases were included: 39 in cohort A and 34 in cohort B. Intracranial response rate was 12% in cohort A; no objective response was reported in patients with brain lesions that were multiple or larger than 1 cm. Median intracranial progression-free survival was 2.7 months (95% CI, 2.3 to 4.6 months) in cohort A and 4.8 months (95% CI, 3.0 to 8.0 months) in cohort B, with adjusted hazard ratio of 2.04 (95% CI, 1.08 to 3.83). Overall survival rate at 12 months was 67% (95% CI, 49.6% to 79.1%) in cohort A and 59% (95% CI, 40.6% to 73.2%) in cohort B. Most patients in cohort A (72%) needed subsequent focal brain therapy. Nivolumab was well tolerated, with no unexpected toxicity. CONCLUSION: Nivolumab activity is limited in patients with untreated brain metastases from ccRCC. Brain imaging and focal therapy should be considered before immune checkpoint inhibitors in patients with metastatic ccRCC.
PURPOSE:Nivolumab is standard of care for patients with metastatic clear cell renal cell carcinoma (ccRCC) after failure of antiangiogenic therapies, but its activity on brain metastases from ccRCC remains unknown, because these patients were excluded from pivotal studies. We aimed to assess the activity of nivolumab in this population. METHODS: The GETUG-AFU 26 NIVOREN phase II trial assessed the activity and safety of nivolumab in patients with metastatic ccRCC who failed vascular endothelial growth factor-directed therapies (ClinicalTrials.gov identifier: NCT03013335). Patients with asymptomatic brain metastases were prospectively identified and underwent dedicated brain evaluation. Two cohorts were constituted: cohort A comprised patients with previously untreated brain metastases, and cohort B comprised patients whose brain metastases underwent prior therapy. The primary end point was intracranial response rate in cohort A. RESULTS: Seventy-three patients with brain metastases were included: 39 in cohort A and 34 in cohort B. Intracranial response rate was 12% in cohort A; no objective response was reported in patients with brain lesions that were multiple or larger than 1 cm. Median intracranial progression-free survival was 2.7 months (95% CI, 2.3 to 4.6 months) in cohort A and 4.8 months (95% CI, 3.0 to 8.0 months) in cohort B, with adjusted hazard ratio of 2.04 (95% CI, 1.08 to 3.83). Overall survival rate at 12 months was 67% (95% CI, 49.6% to 79.1%) in cohort A and 59% (95% CI, 40.6% to 73.2%) in cohort B. Most patients in cohort A (72%) needed subsequent focal brain therapy. Nivolumab was well tolerated, with no unexpected toxicity. CONCLUSION:Nivolumab activity is limited in patients with untreated brain metastases from ccRCC. Brain imaging and focal therapy should be considered before immune checkpoint inhibitors in patients with metastatic ccRCC.
Authors: U Harmenberg; M Lindskog; G Sinclair; M Stenman; H Benmakhlouf; P Wersäll; P Johnstone; M A Hatiboglu; J Mayer-da-Silva Journal: Acta Neurochir (Wien) Date: 2020-09-09 Impact factor: 2.216
Authors: Celina M Crisman; Ankur R Patel; Graham Winston; Cameron W Brennan; Viviane Tabar; Nelson S Moss Journal: World Neurosurg Date: 2020-04-03 Impact factor: 2.104
Authors: Leonidas N Diamantopoulos; Ali R Khaki; Guru P Sonpavde; Vyshak A Venur; Evan Y Yu; Jonathan L Wright; Petros Grivas Journal: Clin Genitourin Cancer Date: 2019-12-05 Impact factor: 2.872
Authors: John H Suh; Rupesh Kotecha; Samuel T Chao; Manmeet S Ahluwalia; Arjun Sahgal; Eric L Chang Journal: Nat Rev Clin Oncol Date: 2020-02-20 Impact factor: 66.675