Robert C, Long G V, Larkin J, Wolchok J D, Hassel J C, Schadendorf D, Hodi F S, Lebbé C, Grob J-J, Hyngstrom J R, Wagstaff J, Chesney J, Butler M O, Bechter O, Márquez-Rodas I, Pavlick A C, Durani P, Pe Benito M, Wang P, Postow M A, Ascierto P A
Gustave Roussy and Paris-Saclay University, Villejuif-Paris Sud, France.
Melanoma Institute Australia, The University of Sydney, and Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia.
Eur J Cancer. 2025 Jan;214:115119. doi: 10.1016/j.ejca.2024.115119. Epub 2024 Nov 16.
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.
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.
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.
Clinical response evaluated in the first months of therapy is a strong predictor of long-term survival, even in patients with poor prognostic biomarkers.
为了研究在3、6或12个月时RECIST反应对长期生存的预测价值，并探索纳武单抗+伊匹木单抗与纳武单抗单药治疗之间的差异，我们分析了CheckMate 069、066和067研究中935例有反应和无反应患者在治疗开始后不同时间点的汇总5年数据。
初治晚期黑色素瘤患者接受纳武单抗+伊匹木单抗或纳武单抗单药治疗。为减少不朽时间偏倚，进行了3个月、6个月或12个月的总生存（OS）和无进展生存（PFS）的标志性分析。通过单因素和多因素分析评估特征与反应之间存在的关联。
纳武单抗+伊匹木单抗在任何时间的反应率为58%（239/409），纳武单抗单药治疗为44%（230/526）。在12个月的标志性分析中，纳武单抗+伊匹木单抗治疗有反应者与无反应者的5年OS率分别为82%和40%（HR=0.23[95%CI，0.15 - 0.35]），纳武单抗单药治疗分别为76%和32%（HR=0.22[95%CI，0.16 - 0.31]）。PFS率分别为83%和32%，以及69%和46%。在3个月和6个月时的反应与5年OS和PFS之间也观察到类似的强关联，超过70%的反应在前3个月观察到。多因素分析显示反应率与基线乳酸脱氢酶（LDH）和程序性死亡受体配体1（PD-L1）状态相关，但即使在LDH高和PD-L1表达低的患者中，标志性分析中反应与长期生存之间的关联仍然存在。
治疗开始后头几个月评估的临床反应是长期生存的有力预测指标，即使对于预后生物标志物较差的患者也是如此。
