Robert J Motzer,Axel Bex,Paul Russo,Yoshihiko Tomita,Hernan Javier Cutuli,Carlos Rojas,Marine Gross-Goupil,Giovanni Schinzari,Bohuslav Melichar,Philippe Barthélémy,Abraham Ruiz Garcia,Jeffrey Sosman,Marc-Oliver Grimm,Jeffrey C Goh,Cristina Suarez,Christian K Kollmannsberger,Suresh G Nair,Brian M Shuch,Jian Huang,Burcin Simsek,Julia Spiridigliozzi,Chung-Wei Lee,Maximiliano van Kooten Losio,Viktor Grünwald
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We report results from part B.\r\n\r\nMETHODS\r\nPatients were randomly assigned (2:1:1) to nivolumab (240 mg once every 2 weeks for up to 12 doses), placebo, or nivolumab (240 mg once every 2 weeks for up to 12 doses) plus ipilimumab (1 mg/kg once every 6 weeks for up to four doses). The planned treatment duration was 24 weeks (approximately 5.5 months). The primary end point was DFS per blinded independent central review (BICR) for nivolumab versus placebo; safety was a secondary end point.\r\n\r\nRESULTS\r\nOverall, 825 patients were randomly assigned to nivolumab (n = 411), placebo (n = 208), or nivolumab plus ipilimumab (n = 206). With a median follow-up of 27.0 months (range, 18.0-42.4), the primary end point of improved DFS per BICR with nivolumab versus placebo was not met (hazard ratio [HR], 0.87 [95% CI, 0.62 to 1.21]; P = .40); the median DFS was not reached in either arm, and 18-month DFS rates were 78.4% versus 75.4%. The HR for DFS per investigator was 0.80 (95% CI, 0.58 to 1.12; P = .19). Grade 3-4 all-cause adverse events (AEs) occurred in 17.2%, 15.0%, and 28.9% of patients with nivolumab, placebo, and nivolumab plus ipilimumab, respectively. Any-grade treatment-related AEs led to discontinuation in 9.6%, 1.0%, and 28.4%, respectively.\r\n\r\nCONCLUSION\r\nPart B of CheckMate 914 did not meet the primary end point of improved DFS for nivolumab versus placebo in patients with localized RCC at high risk of postnephrectomy recurrence.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Adjuvant Nivolumab for Localized Renal Cell Carcinoma at High Risk of Recurrence After Nephrectomy: Part B of the Randomized, Placebo-Controlled, Phase III CheckMate 914 Trial.\",\"authors\":\"Robert J Motzer,Axel Bex,Paul Russo,Yoshihiko Tomita,Hernan Javier Cutuli,Carlos Rojas,Marine Gross-Goupil,Giovanni Schinzari,Bohuslav Melichar,Philippe Barthélémy,Abraham Ruiz Garcia,Jeffrey Sosman,Marc-Oliver Grimm,Jeffrey C Goh,Cristina Suarez,Christian K Kollmannsberger,Suresh G Nair,Brian M Shuch,Jian Huang,Burcin Simsek,Julia Spiridigliozzi,Chung-Wei Lee,Maximiliano van Kooten Losio,Viktor Grünwald\",\"doi\":\"10.1200/jco.24.00773\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"PURPOSE\\r\\nCheckMate 914 is a two-part, randomized phase III trial evaluating adjuvant nivolumab plus ipilimumab (part A) or adjuvant nivolumab monotherapy (part B) versus placebo in mutually exclusive populations of patients with localized renal cell carcinoma (RCC) at high risk of postnephrectomy recurrence. Part A showed no disease-free survival (DFS) benefit for adjuvant nivolumab plus ipilimumab versus placebo. We report results from part B.\\r\\n\\r\\nMETHODS\\r\\nPatients were randomly assigned (2:1:1) to nivolumab (240 mg once every 2 weeks for up to 12 doses), placebo, or nivolumab (240 mg once every 2 weeks for up to 12 doses) plus ipilimumab (1 mg/kg once every 6 weeks for up to four doses). The planned treatment duration was 24 weeks (approximately 5.5 months). The primary end point was DFS per blinded independent central review (BICR) for nivolumab versus placebo; safety was a secondary end point.\\r\\n\\r\\nRESULTS\\r\\nOverall, 825 patients were randomly assigned to nivolumab (n = 411), placebo (n = 208), or nivolumab plus ipilimumab (n = 206). With a median follow-up of 27.0 months (range, 18.0-42.4), the primary end point of improved DFS per BICR with nivolumab versus placebo was not met (hazard ratio [HR], 0.87 [95% CI, 0.62 to 1.21]; P = .40); the median DFS was not reached in either arm, and 18-month DFS rates were 78.4% versus 75.4%. The HR for DFS per investigator was 0.80 (95% CI, 0.58 to 1.12; P = .19). Grade 3-4 all-cause adverse events (AEs) occurred in 17.2%, 15.0%, and 28.9% of patients with nivolumab, placebo, and nivolumab plus ipilimumab, respectively. Any-grade treatment-related AEs led to discontinuation in 9.6%, 1.0%, and 28.4%, respectively.\\r\\n\\r\\nCONCLUSION\\r\\nPart B of CheckMate 914 did not meet the primary end point of improved DFS for nivolumab versus placebo in patients with localized RCC at high risk of postnephrectomy recurrence.\",\"PeriodicalId\":15384,\"journal\":{\"name\":\"Journal of Clinical Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":42.1000,\"publicationDate\":\"2024-09-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/jco.24.00773\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/jco.24.00773","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
PURPOSECheckMate 914是一项由两部分组成的随机III期试验,评估尼妥珠单抗联合伊匹单抗辅助疗法(A部分)或尼妥珠单抗单药辅助疗法(B部分)与安慰剂在肾切除术后复发风险较高的局部肾细胞癌(RCC)患者中的互斥性。A部分结果显示,尼妥珠单抗加伊匹单抗辅助治疗与安慰剂相比没有无病生存期(DFS)获益。我们报告了B部分的结果。方法将患者随机分配(2:1:1)至尼韦单抗(240毫克,每2周1次,最多12次)、安慰剂或尼韦单抗(240毫克,每2周1次,最多12次)加伊匹单抗(1毫克/公斤,每6周1次,最多4次)。计划疗程为24周(约5.5个月)。结果总计有825名患者被随机分配到尼伐单抗(411例)、安慰剂(208例)或尼伐单抗加伊匹单抗(206例)治疗。中位随访时间为27.0个月(18.0-42.4个月),nivolumab与安慰剂相比,每个BICR的DFS均有所改善,但未达到主要终点(危险比[HR],0.87[95% CI,0.62-1.21];P = .40);两组均未达到中位DFS,18个月DFS率分别为78.4%和75.4%。每位研究者的 DFS HR 为 0.80 (95% CI, 0.58 to 1.12; P = .19)。使用尼妥珠单抗、安慰剂和尼妥珠单抗加伊匹单抗的患者中,分别有17.2%、15.0%和28.9%发生了3-4级全因不良事件(AEs)。结论在肾切除术后复发风险较高的局部RCC患者中,CheckMate 914的B部分未达到尼妥珠单抗与安慰剂相比改善DFS的主要终点。
Adjuvant Nivolumab for Localized Renal Cell Carcinoma at High Risk of Recurrence After Nephrectomy: Part B of the Randomized, Placebo-Controlled, Phase III CheckMate 914 Trial.
PURPOSE
CheckMate 914 is a two-part, randomized phase III trial evaluating adjuvant nivolumab plus ipilimumab (part A) or adjuvant nivolumab monotherapy (part B) versus placebo in mutually exclusive populations of patients with localized renal cell carcinoma (RCC) at high risk of postnephrectomy recurrence. Part A showed no disease-free survival (DFS) benefit for adjuvant nivolumab plus ipilimumab versus placebo. We report results from part B.
METHODS
Patients were randomly assigned (2:1:1) to nivolumab (240 mg once every 2 weeks for up to 12 doses), placebo, or nivolumab (240 mg once every 2 weeks for up to 12 doses) plus ipilimumab (1 mg/kg once every 6 weeks for up to four doses). The planned treatment duration was 24 weeks (approximately 5.5 months). The primary end point was DFS per blinded independent central review (BICR) for nivolumab versus placebo; safety was a secondary end point.
RESULTS
Overall, 825 patients were randomly assigned to nivolumab (n = 411), placebo (n = 208), or nivolumab plus ipilimumab (n = 206). With a median follow-up of 27.0 months (range, 18.0-42.4), the primary end point of improved DFS per BICR with nivolumab versus placebo was not met (hazard ratio [HR], 0.87 [95% CI, 0.62 to 1.21]; P = .40); the median DFS was not reached in either arm, and 18-month DFS rates were 78.4% versus 75.4%. The HR for DFS per investigator was 0.80 (95% CI, 0.58 to 1.12; P = .19). Grade 3-4 all-cause adverse events (AEs) occurred in 17.2%, 15.0%, and 28.9% of patients with nivolumab, placebo, and nivolumab plus ipilimumab, respectively. Any-grade treatment-related AEs led to discontinuation in 9.6%, 1.0%, and 28.4%, respectively.
CONCLUSION
Part B of CheckMate 914 did not meet the primary end point of improved DFS for nivolumab versus placebo in patients with localized RCC at high risk of postnephrectomy recurrence.
期刊介绍:
The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.