Anderson Carryn, Salvaggio Samuel, De Backer Mickaël, Chiem Jean-Christophe, Walker Gary, Saunders Deborah, Lee Christopher M, Dunlap Neal, Kennedy Eugene, Beardsley Robert, Schoen Benton, Buyse Marc
Department of Radiation Oncology University of Iowa Hospitals & Clinics, Iowa City, Iowa.
International Drug Development Institute (IDDI), Louvain-la-Neuve, Belgium.
Adv Radiat Oncol. 2024 Nov 9;10(1):101674. doi: 10.1016/j.adro.2024.101674. eCollection 2025 Jan.
Oral mucositis (OM) is a debilitating side effect of cisplatin and intensity-modulated radiation therapy (IMRT) in patients with head and neck cancer. The phase 3 ROMAN trial showed avasopasem manganese (AVA) significantly decreased individual endpoints of incidence and duration of severe oral mucositis (SOM, World Health Organization [WHO] grade 3-4), with nominal decrease in severity (WHO grade 4) and significant increase in the delay in onset of SOM. We sought to determine the Net Treatment Benefit (NTB) of AVA versus placebo (PBO) using the generalized pairwise comparisons (GPC) method.
GPC is a statistical method that permits simultaneous analysis of several prioritized outcomes, comparing all possible pairs of a patient in the active (ie, AVA) group and a patient from the control (ie, PBO) group. NTB is the net benefit across all the outcomes for AVA compared to PBO. Key clinically relevant outcomes from ROMAN were prioritized: (1) WHO grade 4 OM incidence; (2) SOM incidence; (3) days of SOM; (4) days to SOM onset, with 7 days difference defined as the clinical relevance threshold for SOM days and SOM onset.
GPC analysis of 407 patients (AVA = 241, placebo = 166) stratified by cisplatin schedule and treatment setting resulted in 13,969 pairwise comparisons. AVA showed statistically significant net benefit on all 4 key outcomes with a 53.9% probability that AVA would benefit patients versus a 35.0% probability that PBO would; the difference between these probabilities was a NTB of 18.9% ( = .0012), translating to an AVA number needed to treat of 5.3 patients. All outcomes contributed to NTB, reflecting improvements in SOM incidence, onset and duration, and in grade 4 OM incidence seen in the original ROMAN analysis.
This GPC analysis shows compelling evidence from the ROMAN trial of AVA's clinical benefit across key parameters of SOM burden.
口腔黏膜炎（OM）是头颈癌患者接受顺铂和调强放射治疗（IMRT）时出现的一种使人衰弱的副作用。3期ROMAN试验表明，avasopasem锰（AVA）显著降低了严重口腔黏膜炎（SOM，世界卫生组织[WHO]3 - 4级）的发生率和持续时间等个体终点指标，严重程度（WHO 4级）有一定程度降低，SOM发病延迟显著增加。我们试图使用广义成对比较（GPC）方法确定AVA与安慰剂（PBO）相比的净治疗效益（NTB）。
GPC是一种统计方法，允许同时分析多个优先结果，比较活性（即AVA）组中的一名患者与对照（即PBO）组中的一名患者的所有可能配对。NTB是AVA与PBO相比在所有结果上的净效益。对ROMAN试验中关键的临床相关结果进行了优先排序：（1）WHO 4级OM发生率；（2）SOM发生率；（3）SOM天数；（4）SOM发病天数，将7天的差异定义为SOM天数和SOM发病的临床相关阈值。
根据顺铂给药方案和治疗设置对407例患者（AVA = 241例，安慰剂 = 166例）进行GPC分析，得到13969对配对比较。AVA在所有4个关键结果上均显示出统计学上显著的净效益，AVA使患者受益的概率为53.9%，而PBO为35.0%；这些概率之间的差异即NTB为18.9%（P = 0.0012），这意味着AVA每治疗5.3例患者就有1例受益。所有结果都对NTB有贡献，反映了在原始ROMAN分析中观察到的SOM发生率、发病和持续时间以及4级OM发生率的改善。
这项GPC分析显示了来自ROMAN试验的有力证据，证明AVA在SOM负担的关键参数方面具有临床益处。
