Weber Jeffrey S, Middleton Mark R, Yates Georgia, Sharpe Daniel J, Kurt Murat, Lobo Maurice, Moshyk Andriy, Vanderpuye-Orgle Jacqueline, Mohr Peter
New York University Perlmutter Cancer Center, New York, NY.
Deceased.
J Clin Oncol. 2025 Mar 10;43(8):929-937. doi: 10.1200/JCO.24.00237. Epub 2024 Oct 8.
Standard-of-care treatments for patients with resected stage III/IV melanoma include the immuno-oncology (IO) agents nivolumab (NIVO) and ipilimumab (IPI). This study used mixture cure models (MCMs) to estimate cure rates among patients treated with NIVO or IPI in the phase III CheckMate 238 (ClinicalTrials.gov identifier: NCT02388906) and European Organization for Research and Treatment of Cancer (EORTC) 18071 (ClinicalTrials.gov identifier: NCT00636168) trials, and to assess the impact of use of adjuvant immunotherapy on cure rates versus watchful waiting.
MCMs were applied to patient-level recurrence-free survival data from CheckMate 238 and EORTC 18071. Cured patients were assumed to experience no disease recurrence and mortality risks similar to the general population. Uncured patients were at risk of disease recurrence and all-cause death. The survival trend of the cured patients was estimated using life expectancy data for a general population with the same baseline demographic characteristics. A regression model assessed the odds ratios (ORs) of cure across key subgroups on the basis of baseline characteristics of the study populations.
In CheckMate 238, estimated cure rates were 48.3% (95% CI, 41.8 to 54.9) with NIVO and 38.2% (95% CI, 32.7 to 44.1) with IPI. In EORTC 18071, estimated cure rates were 38.0% (95% CI, 32.1 to 44.2) with IPI and 29.2% (95% CI, 24.4 to 34.6) with placebo. In the indirect comparison of the two trials, the odds of cure were significantly higher with NIVO than with placebo (OR, 2.33 [95% CI, 1.49 to 3.65]).
Analyses involving two large phase III trials investigating adjuvant IO treatment for resected melanoma demonstrate higher cure rates for both NIVO and IPI than placebo, with NIVO providing the highest cure rate. Similar cure rates were estimated for patients treated with IPI in both trials, despite staging and dosing differences.
对于已切除的III/IV期黑色素瘤患者，标准治疗方案包括免疫肿瘤学（IO）药物纳武利尤单抗（NIVO）和伊匹木单抗（IPI）。本研究使用混合治愈模型（MCM）来估计在III期CheckMate 238（ClinicalTrials.gov标识符：NCT02388906）和欧洲癌症研究与治疗组织（EORTC）18071（ClinicalTrials.gov标识符：NCT00636168）试验中接受NIVO或IPI治疗的患者的治愈率，并评估辅助免疫治疗的使用与观察等待相比对治愈率的影响。
将MCM应用于CheckMate 238和EORTC 18071患者水平的无复发生存数据。假定治愈的患者不会出现疾病复发，且死亡风险与一般人群相似。未治愈的患者有疾病复发和全因死亡的风险。使用具有相同基线人口统计学特征的一般人群的预期寿命数据估计治愈患者的生存趋势。一个回归模型根据研究人群的基线特征评估关键亚组中治愈的优势比（OR）。
在CheckMate 238中，NIVO的估计治愈率为48.3%（95%CI，41.8至54.9），IPI为38.2%（95%CI，32.7至44.1）。在EORTC 18071中，IPI的估计治愈率为38.0%（95%CI，32.1至44.2），安慰剂为29.2%（95%CI，24.4至34.6）。在两项试验的间接比较中，NIVO治愈的几率显著高于安慰剂（OR，2.33[95%CI，1.49至3.65]）。
涉及两项大型III期试验的分析，这些试验研究了辅助IO治疗已切除黑色素瘤的情况，结果表明NIVO和IPI的治愈率均高于安慰剂，其中NIVO的治愈率最高。尽管分期和给药存在差异，但两项试验中接受IPI治疗的患者估计治愈率相似。
