S. Stintzing , J. Tabernero , T. Satoh , A. Dasari , S. Lonardi , C. Eng , R. Garcia-Carbonero , E. Elez , T. Yoshino , A.F. Sobrero , J.C. Yao , S. Kasper , D. Arnold , E. Basic , M. Granold , M. Petschulies , L. Wu , Y.-C. Chung , L. Chen , Z. Yang , E. Van Cutsem
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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, <em>P</em> < 0.001]. This <em>post hoc</em> Q-TWiST analysis compared the benefit–risk of fruquintinib versus placebo in all patients randomized in FRESCO-2.</div></div><div><h3>Methods</h3><div>Patients with refractory mCRC in the USA, Europe, Japan, and Australia were randomized to receive fruquintinib (<em>n</em> = 461) or placebo (<em>n</em> = 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). 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引用次数: 0
摘要
转移性结直肠癌（mCRC）的治疗毒性和疾病相关症状可对生活质量（QoL）产生不利影响。维持生活质量是改善生存结果的重要治疗目标。无疾病症状或毒性的质量调整时间（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研究达到了主要终点，显示fruquininib +最佳支持治疗（BSC）优于安慰剂+ BSC的总生存率[风险比0.66,95%可信区间（CI） 0.55-0.80, P <；0.001]。这项事后Q-TWiST分析比较了FRESCO-2随机分组的所有患者中fruquininib与安慰剂的获益-风险。方法美国、欧洲、日本和澳大利亚的难治性mCRC患者随机接受fruquintinib （n = 461）或安慰剂（n = 230）加BSC治疗，直到疾病进展或不可接受的毒性。患者的生存时间划分如下：从随机分配到进展前3/4级治疗不良事件（teae）的时间（TOX）；从随机分组到无3/4级teae （TWiST）的进展时间；以及从进展到死亡/审查（REL）的时间。假设TWiST的效用系数为1，TOX和rel的效用系数为0.5，Q-TWiST计算为每种健康状态的综合效用加权平均持续时间。结果在BSC中加入fruquininib（相对于安慰剂）后，Q-TWiST得到改善，治疗间差异为2.0个月(95% CI为1.5-2.6个月，P <；0.05)，相对改善31.4%。这种影响主要是由TWiST成分的差异所驱动的[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是一致的，包括年龄、性别、肝转移和原发肿瘤部位。亚组分析和敏感性分析结果证实了初步分析结果的稳健性。结论：与安慰剂相比，fruquininib在难治性mCRC中提供了具有临床意义的质量调整生存获益。
Quality-adjusted survival in patients with metastatic colorectal cancer treated with fruquintinib plus best supportive care: results from FRESCO-2
Background
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.
Methods
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.
Results
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.
Conclusions
Fruquintinib provides a clinically meaningful quality-adjusted survival benefit versus placebo in refractory mCRC.
期刊介绍：
ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research.
ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO.
Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.
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