■有兴趣在肿瘤学中使用治疗中断,减少毒性而不影响疗效。
■AII/III期多中心,开放标签,平行组,评估肾细胞癌患者治疗中断的随机对照非劣效性试验。
■局部晚期或转移性肾细胞癌患者,在英国国家卫生服务医院开始使用酪氨酸激酶抑制剂作为一线治疗。
■在试用时,患者被随机(1:1)接受无药间期策略或常规延续策略.舒尼替尼/帕唑帕尼治疗24周后,无药间期策略患者接受治疗中断,直至疾病进展,其他中断取决于疾病反应和患者选择.常规延续策略患者继续治疗。两种试验策略都持续到治疗不耐受,疾病进展的治疗,退出或死亡。
■确定无药物间隔策略在总生存期和质量调整生命年的共同主要结果方面是否不劣于常规延续策略。
■为了得出非劣效性,在意向治疗和符合方案的分析中,总生存率均需要≤7.5%,质量调整寿命年均需要≤10%.这相当于估计的95%置信区间分别高于0.812和-0.156。使用EuroQol-5维度问卷的效用指数计算质量调整生命年。
■将九百二十名患者随机分组(461例常规延续策略与459无药间隔策略)从2012年1月13日至2017年9月12日。试验治疗和随访于2020年12月31日停止。488例(53.0%)患者[240例(52.1%)与248(54.0%)]在第24周后继续试验。中位治疗-中断长度为87天。9119例患者被纳入意向治疗分析(461例与458)和871例患者在符合方案分析中(453例vs.418).对于总体生存率,在意向治疗分析中得出非劣效性,但在符合方案分析中得出非劣效性[风险比(95%置信区间)意向治疗0.97(0.83至1.12);符合方案0.94(0.80至1.09)非劣效性界限:95%置信区间≥0.812,意向治疗:0.83>0.812非劣性,符合方案:0.80<0.812不劣质]。因此,在总生存期方面,无药物间期策略未得出结论不劣于常规延续策略.对于质量调整的寿命年,在意向治疗和符合方案分析中均得出非劣效性[边际效应(95%置信区间)意向治疗-0.05(-0.15~0.05);符合方案0.04(-0.14~0.21)非劣效性界限:95%置信区间≥-0.156].因此,研究认为,无药物间期策略在质量调整寿命年方面不劣于常规延续策略.
■该研究的主要局限性是总生存事件少于预期,导致非劣效性比较的权力降低。
■未来的研究应该研究肾细胞癌的治疗中断与更现代的治疗方法。
■对质量调整后的寿命年终点显示非劣效性,但对预先定义的总生存期未显示。然而,尽管未达到方案的非劣效性的主要终点,这项研究表明,治疗中断策略可能不会显著降低预期寿命,不降低生活质量,具有经济效益。虽然治疗临床医生的观点没有正式收集,临床医生长期招募了大量患者,这一事实提示了这项研究的支持,并提供了明确的证据,证明接受酪氨酸激酶抑制剂治疗的肾细胞癌患者的治疗中断策略是可行的.
■本试验注册为ISRCTN06473203。
■该奖项由美国国家卫生与护理研究所(NIHR)卫生技术评估计划(NIHR奖项编号:09/91/21)资助,并在《卫生技术评估》中全文发布;卷。28号45.有关更多奖项信息,请参阅NIHR资助和奖励网站。
癌症的治疗中断对患者和卫生专业人员非常感兴趣。肾细胞癌是最常见的肾癌类型。舒尼替尼和帕唑帕尼都是靶向治疗。它们通常用于治疗晚期肾癌,但经常引起副作用,有时需要使用减少剂量甚至停止治疗。STAR试验旨在观察计划的治疗中断是否使接受舒尼替尼和帕唑帕尼治疗的晚期肾癌患者感觉更好,而不会严重影响治疗效果。治疗24周后,患者服用舒尼替尼和帕唑帕尼,要么按正常方式服用,要么选择计划中断治疗.继续以这种方式治疗患者,直到药物相关的副作用停止治疗,患者在接受治疗时病情恶化或患者死亡。该试验比较了不同治疗策略在患者寿命和这段时间内的生活质量方面的效果。该试验是英国最大的晚期肾细胞癌试验。2012年至2017年期间,来自60个英国中心的患者参加。它由国家卫生与护理研究所卫生技术评估计划资助,并由利兹临床试验研究部门运营。总的来说,920名患者参加。4161名患者被分配继续治疗,459名患者被分配开始至少一次治疗中断。治疗中断平均持续87天。患者在试验的两组中生活的时间长度相似,但是由于信息不足,这无法得出结论。被分配治疗中断而不是继续治疗不会对患者的生活质量产生负面影响。此外,与仅继续治疗相比,为患者分配治疗休息时间可显著节省费用.重要的计划治疗中断被证明是可行的。
UNASSIGNED: There is interest in using treatment breaks in oncology, to reduce toxicity without compromising efficacy.
UNASSIGNED: A Phase II/III multicentre, open-label, parallel-group, randomised controlled non-inferiority trial assessing treatment breaks in patients with renal cell carcinoma.
UNASSIGNED: Patients with locally advanced or metastatic renal cell carcinoma, starting tyrosine kinase inhibitor as first-line treatment at United Kingdom National Health Service hospitals.
UNASSIGNED: At trial entry, patients were randomised (1 : 1) to a drug-free interval strategy or a conventional continuation strategy. After 24 weeks of treatment with sunitinib/pazopanib, drug-free interval strategy patients took up a treatment break until disease progression with additional breaks dependent on disease response and patient choice. Conventional continuation strategy patients continued on treatment. Both trial strategies continued until treatment intolerance, disease progression on treatment, withdrawal or death.
UNASSIGNED: To determine if a drug-free interval strategy is non-inferior to a conventional continuation strategy in terms of the co-primary outcomes of overall survival and quality-adjusted life-years.
UNASSIGNED: For non-inferiority to be concluded, a margin of ≤ 7.5% in overall survival and ≤ 10% in quality-adjusted life-years was required in both intention-to-treat and per-protocol analyses. This equated to the 95% confidence interval of the estimates being above 0.812 and -0.156, respectively. Quality-adjusted life-years were calculated using the utility index of the EuroQol-5 Dimensions questionnaire.
UNASSIGNED: Nine hundred and twenty patients were randomised (461 conventional continuation strategy vs. 459 drug-free interval strategy) from 13 January 2012 to 12 September 2017. Trial treatment and follow-up stopped on 31 December 2020. Four hundred and eighty-eight (53.0%) patients [240 (52.1%) vs. 248 (54.0%)] continued on trial post week 24. The median treatment-break length was 87 days. Nine hundred and nineteen patients were included in the intention-to-treat analysis (461 vs. 458) and 871 patients in the per-protocol analysis (453 vs. 418). For overall survival, non-inferiority was concluded in the intention-to-treat analysis but not in the per-protocol analysis [hazard ratio (95% confidence interval) intention to treat 0.97 (0.83 to 1.12); per-protocol 0.94 (0.80 to 1.09) non-inferiority margin: 95% confidence interval ≥ 0.812, intention to treat: 0.83 > 0.812 non-inferior, per-protocol: 0.80 < 0.812 not non-inferior]. Therefore, a drug-free interval strategy was not concluded to be non-inferior to a conventional continuation strategy in terms of overall survival. For quality-adjusted life-years, non-inferiority was concluded in both the intention-to-treat and per-protocol analyses [marginal effect (95% confidence interval) intention to treat -0.05 (-0.15 to 0.05); per-protocol 0.04 (-0.14 to 0.21) non-inferiority margin: 95% confidence interval ≥ -0.156]. Therefore, a drug-free interval strategy was concluded to be non-inferior to a conventional continuation strategy in terms of quality-adjusted life-years.
UNASSIGNED: The main limitation of the study is the fewer than expected overall survival events, resulting in lower power for the non-inferiority comparison.
UNASSIGNED: Future studies should investigate treatment breaks with more contemporary treatments for renal cell carcinoma.
UNASSIGNED: Non-inferiority was shown for the quality-adjusted life-year end point but not for overall survival as pre-defined. Nevertheless, despite not meeting the primary end point of non-inferiority as per protocol, the study suggested that a treatment-break strategy may not meaningfully reduce life expectancy, does not reduce quality of life and has economic benefits. Although the treating clinicians\' perspectives were not formally collected, the fact that clinicians recruited a large number of patients over a long period suggests support for the study and provides clear evidence that a treatment-break strategy for patients with renal cell carcinoma receiving tyrosine kinase inhibitor therapy is feasible.
UNASSIGNED: This trial is registered as ISRCTN06473203.
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Programme (NIHR award ref: 09/91/21) and is published in full in Health Technology Assessment; Vol. 28, No. 45. See the NIHR Funding and Awards website for further award information.
Treatment breaks in cancer are of significant interest to patients and health professionals. Renal cell carcinoma is the most common type of kidney cancer. Sunitinib and pazopanib are both targeted treatments. They were commonly used to treat advanced kidney cancer but often cause side effects, sometimes requiring use of a reduced dose or even stopping treatment. The STAR trial was designed to see whether planned treatment breaks made patients with advanced kidney cancer being treated with sunitinib and pazopanib feel better, without substantially affecting how well the treatment worked. After 24 weeks of treatment, patients took sunitinib and pazopanib either as they normally would or in the alternative way with planned treatment breaks. Treating patients in this way was continued until drug-related side effects stopped treatment, patients’ disease worsened while taking treatment or the patient died. The trial compared how well the different treatment strategies worked in terms of how long patients lived and their quality of life over that time. This trial is the largest United Kingdom trial in advanced renal cell carcinoma. Patients took part from 60 United Kingdom centres between 2012 and 2017. It was funded by the National Institute for Health and Care Research Health Technology Assessment Programme and run by the Leeds Clinical Trials Research Unit. In total, 920 patients took part. Four hundred and sixty-one patients were allocated to continue treatment and 459 were allocated to start at least one treatment break. Treatment breaks lasted on average 87 days. The length of time patients lived in both arms of the trial appeared similar, but this cannot be concluded due to insufficient information. Being allocated to have treatment breaks rather than continuing treatment did not negatively impact a patient’s quality of life. Additionally, allocating patients to have treatment breaks was shown to have significant cost savings compared to just continuing treatment. Importantly planned treatment breaks were shown to be feasible.