Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019
Safety and Efficacy of Nivolumab in Brain Metastases From Renal Cell Carcinoma: Results of the GETUG-AFU 26 NIVOREN Multicenter Phase II Study.
Клиническое исследование II фазыСтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Flippot Ronan, Dalban Cécile, Laguerre Brigitte, Borchiellini Delphine, Gravis Gwénaelle, Négrier Sylvie, Chevreau Christine, Joly Florence, Geoffrois Lionnel, Ladoire Sylvain, Mahammedi Hakim, Rolland Frédéric, Gross-Goupil Marine, Deluche Elise, Priou Frank, Laramas Mathieu, Barthélémy Philippe, Narciso Bérengère, Houedé Nadine, Culine Stéphane, Oudard Stéphane, Chenot Marina, Tantot Florence, Chabaud Sylvie, Escudier Bernard, Albiges Laurence
Аннотация
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.
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.