Stintzing S, Tabernero J, Satoh T, Dasari A, Lonardi S, Eng C, Garcia-Carbonero R, Elez E, Yoshino T, Sobrero A F, Yao J C, Kasper S, Arnold D, Basic E, Granold M, Petschulies M, Wu L, Chung Y-C, Chen L, Yang Z, Van Cutsem E
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Hematology, Oncology and Cancer Immunology (CCM), Berlin, Germany.
Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology, Centro Cellex, Barcelona, Spain.
ESMO Open. 2025 Mar;10(3):104297. doi: 10.1016/j.esmoop.2025.104297. Epub 2025 Feb 21.
Treatment toxicity and disease-related symptoms of metastatic colorectal cancer (mCRC) can adversely affect quality of life (QoL). Maintaining QoL is an important treatment goal alongside improving survival outcomes. Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) measures the quality of patients' survival by assessing the proportion of survival time that is free of symptoms/toxicity. The phase III FRESCO-2 study met its primary endpoint, demonstrating improved overall survival with fruquintinib plus best supportive care (BSC) versus placebo plus BSC [hazard ratio 0.66, 95% confidence interval (CI) 0.55-0.80, P < 0.001]. This post hoc Q-TWiST analysis compared the benefit-risk of fruquintinib versus placebo in all patients randomized in FRESCO-2.
Patients with refractory mCRC in the USA, Europe, Japan, and Australia were randomized to receive fruquintinib (n = 461) or placebo (n = 230) plus BSC until disease progression or unacceptable toxicity. Patients' survival time was partitioned as follows: time from randomization with grade 3/4 treatment-emergent adverse events (TEAEs) before progression (TOX); time from randomization to progression without grade 3/4 TEAEs (TWiST); and time from progression to death/censoring (REL). Q-TWiST was calculated as the combined utility-weighted mean durations of each health state, assuming utility coefficients of 1 for TWiST and 0.5 for TOX and REL.
Q-TWiST was improved when fruquintinib (versus placebo) was added to BSC, with a between-treatment difference of 2.0 months (95% CI 1.5-2.6 months, P < 0.05) and a relative improvement of 31.4%. This effect was primarily driven by the difference in the TWiST component [mean difference 2.1 months (95% CI 1.8-2.5 months), P < 0.05]. Q-TWiST improvements were consistent in all subgroups, including by age, sex, liver metastases, and primary tumor site. The subgroup and sensitivity analysis results confirmed the robustness of the primary analysis findings.
Fruquintinib provides a clinically meaningful quality-adjusted survival benefit versus placebo in refractory mCRC.
转移性结直肠癌（mCRC）的治疗毒性和疾病相关症状会对生活质量（QoL）产生不利影响。维持生活质量是与改善生存结果同样重要的治疗目标。质量调整无疾病或毒性症状时间（Q-TWiST）通过评估无症状/毒性的生存时间比例来衡量患者的生存质量。III期FRESCO-2研究达到了其主要终点，显示呋喹替尼联合最佳支持治疗（BSC）对比安慰剂联合BSC可改善总生存期[风险比0.66，95%置信区间（CI）0.55 - 0.80，P < 0.001]。这项事后Q-TWiST分析比较了呋喹替尼与安慰剂在FRESCO-2研究中所有随机分组患者中的获益风险。
在美国、欧洲、日本和澳大利亚的难治性mCRC患者被随机分配接受呋喹替尼（n = 461）或安慰剂（n = 230）联合BSC，直至疾病进展或出现不可接受的毒性。患者的生存时间分为以下几部分：随机分组后至疾病进展前出现3/4级治疗中出现的不良事件（TEAE）的时间（TOX）；随机分组至无3/4级TEAE的疾病进展时间（TWiST）；以及疾病进展至死亡/删失的时间（REL）。Q-TWiST计算为每个健康状态的效用加权平均持续时间之和，假设TWiST的效用系数为1，TOX和REL的效用系数为0.5。
将呋喹替尼（对比安慰剂）添加到BSC中可改善Q-TWiST，治疗组间差异为2.0个月（95% CI 1.5 - 2.6个月，P < 0.05），相对改善率为31.4%。这种效果主要由TWiST部分的差异驱动[平均差异2.1个月（95% CI 1.8 - 2.5个月），P < 0.05]。Q-TWiST的改善在所有亚组中均一致，包括按年龄、性别、肝转移和原发肿瘤部位划分的亚组。亚组和敏感性分析结果证实了主要分析结果的稳健性。
在难治性mCRC中，呋喹替尼对比安慰剂可提供具有临床意义的质量调整生存获益。
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