Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2024-11-16 DOI:10.1016/j.ejca.2024.115119

C. Robert , G.V. Long , J. Larkin , J.D. Wolchok , J.C. Hassel , D. Schadendorf , F.S. Hodi , C. Lebbé , J.-J. Grob , J.R. Hyngstrom , J. Wagstaff , J. Chesney , M.O. Butler , O. Bechter , I. Márquez-Rodas , A.C. Pavlick , P. Durani , M. Pe Benito , P. Wang , M.A. Postow , P.A. Ascierto

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引用次数: 0

Abstract

Purpose

To investigate the predictive value of RECIST response within 3, 6, or 12 months on long-term survival, and explore differences between nivolumab+ipilimumab and nivolumab monotherapy, we analyzed pooled 5-year data of 935 responder and non-responder patients at various time points after treatment initiation in CheckMate 069, 066, and 067 studies.

Patients and methods

Treatment-naive advanced melanoma patients received nivolumab+ipilimumab or nivolumab monotherapy. To decrease immortal time bias, 3-, 6-, or 12-month overall survival (OS) and progression-free survival (PFS) landmark analyses were performed. Association between characteristics and response was evaluated by univariate and multivariate analyses.

Results

Response rates at any time were 58 % (239/409) for nivolumab+ipilimumab and 44 % (230/526) for nivolumab monotherapy. In 12-month landmark analyses, 5-year OS rates for responders versus non-responders were 82 % versus 40 % with nivolumab+ipilimumab (HR=0.23 [95 % CI, 0.15–0.35]) and 76 % versus 32 % with nivolumab monotherapy (HR=0.22 [95 % CI, 0.16–0.31]). PFS rates were 83 % versus 32 % and 69 % versus 46 %, respectively. Similar strong associations between response at 3 and 6 months and 5-year OS and PFS were also observed with more than 70 % of the responses observed in the first 3 months. Response rates correlated with baseline LDH and PD-L1 status by multivariate analysis but the association between response and long-term survival was maintained in landmark analyses even among patients with high LDH and low PD-L1 expression.

Conclusion

Clinical response evaluated in the first months of therapy is a strong predictor of long-term survival, even in patients with poor prognostic biomarkers.

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尼妥珠单抗联合伊匹单抗或尼妥珠单抗单药治疗第一年内应答患者的长期疗效：对935名患者的汇总分析

目的为了研究3、6或12个月内的RECIST应答对长期生存的预测价值，并探讨nivolumab+ipilimumab和nivolumab单药治疗之间的差异，我们分析了CheckMate 069、066和067研究中935名应答和非应答患者在治疗开始后不同时间点的5年汇总数据。患者和方法未经治疗的晚期黑色素瘤患者接受了nivolumab+ipilimumab或nivolumab单药治疗。为减少不死时间偏倚，进行了3、6或12个月的总生存期（OS）和无进展生存期（PFS）地标分析。结果nivolumab+ipilimumab在任何时间的应答率为58%（239/409），nivolumab单药为44%（230/526）。在为期12个月的地标分析中，nivolumab+ipilimumab的5年OS率为82%对40%（HR=0.23 [95 % CI, 0.15-0.35]），nivolumab单药疗法的5年OS率为76%对32%（HR=0.22 [95 % CI, 0.16-0.31]）。PFS率分别为83%对32%和69%对46%。3个月和6个月的应答与5年OS和PFS之间也有类似的密切联系，70%以上的应答是在前3个月观察到的。通过多变量分析，应答率与基线 LDH 和 PD-L1 状态相关，但即使在高 LDH 和低 PD-L1 表达的患者中，应答与长期生存之间的关联在地标分析中也保持不变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.