Hamers Patricia A H, Vink Geraldine R, Elferink Marloes A G, Stellato Rebecca K, Dijksterhuis Willemieke P M, Punt Cornelis J A, Koopman Miriam, May Anne M
Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Netherlands Comprehensive Cancer Organisation, Department of Research and Development, Utrecht, the Netherlands.
Clin Colorectal Cancer. 2022 Jun;21(2):154-166. doi: 10.1016/j.clcc.2022.03.002. Epub 2022 Mar 24.
The RECOURSE trial demonstrated a modest benefit in overall survival (OS) for trifluridine/tipiracil (FTD/TPI) versus placebo in pretreated metastatic colorectal cancer (mCRC) patients. Unfortunately, quality of life (QoL) was not assessed. We evaluated QoL and survival of patients treated with FTD/TPI in daily practice.
QUALITAS is a substudy of the Prospective Dutch CRC cohort (PLCRC). From 150 mCRC patients treated with FTD/TPI, QoL (EORTC QLQ-C30 and QLQ-CR29) was assessed monthly from study entry, and linked to clinical data of the Netherlands Cancer Registry. Joint models were constructed combining mixed effects models with Cox PH models. Primary endpoint was difference in QoL over time (which was deemed clinically relevant if ≥10 points). Secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF), and OS. We analyzed the association between QLQ-C30 Summary Score (QoL-SS) at FTD/TPI initiation (baseline) and survival.
There was no clinically relevant change in QoL-SS from baseline to 10 months post-baseline (i.e. the cut-off point after which 90% of patients had discontinued FTD/TPI treatment): -5.3 [95% CI -8.7;-1.5]. Patients who were treated with FTD/TPI for ≥ 3 months (n = 85) reported 6.3 [1.6;11.1] points higher baseline QoL, compared to patients treated < 3 months (n = 65, "poor responders"). In the latter, time to a clinically relevant QoL deterioration was < 2 months. Median PFS, TTF and OS were 2.9 [2.7;3.1], 3.1 [2.9;3.2] and 7.7 [6.6;8.8] months, respectively. Worse baseline QoL-SS was independently associated with shorter OS (HR 0.45 [0.32;0.63]), PFS (0.63 [0.48;0.83]), and TTF (0.64 [0.47;0.86]).
The maintenance of QoL during FTD/TPI treatment in daily practice supports its use. The QoL deterioration in "poor responders" is likely due to disease progression. The strong association between worse baseline QoL and shorter survival suggests that clinicians should take QoL into account when determining prognosis and treatment strategy for individual patients.
RECOURSE试验表明，在既往接受过治疗的转移性结直肠癌（mCRC）患者中，三氟尿苷/替匹嘧啶（FTD/TPI）对比安慰剂在总生存期（OS）方面有适度获益。遗憾的是，未评估生活质量（QoL）。我们评估了在日常实践中接受FTD/TPI治疗的患者的生活质量和生存情况。
QUALITAS是荷兰前瞻性结直肠癌队列（PLCRC）的一项子研究。从150例接受FTD/TPI治疗的mCRC患者中，自研究入组起每月评估生活质量（欧洲癌症研究与治疗组织核心量表QLQ-C30和结直肠癌特异性量表QLQ-CR29），并与荷兰癌症登记处的临床数据相关联。构建联合模型，将混合效应模型与Cox PH模型相结合。主要终点是生活质量随时间的差异（如果≥10分则被认为具有临床相关性）。次要终点是无进展生存期（PFS）、治疗失败时间（TTF）和总生存期。我们分析了FTD/TPI开始治疗时（基线）的QLQ-C30总结评分（QoL-SS）与生存之间的关联。
从基线到基线后10个月（即90%的患者停止FTD/TPI治疗后的截止点），QoL-SS没有具有临床相关性的变化：-5.3 [95%可信区间-8.7；-1.5]。接受FTD/TPI治疗≥3个月的患者（n = 85）报告的基线生活质量比治疗<3个月的患者（n = 65，“反应不佳者”）高6.3 [1.6；11.1]分。在后者中，出现具有临床相关性的生活质量恶化的时间<2个月。中位PFS、TTF和OS分别为2.9 [2.7；3.1]、3.1 [2.9；3.2]和7.7 [6.6；8.8]个月。较差的基线QoL-SS与较短的OS（风险比0.45 [0.32；0.63]）、PFS（0.63 [0.48；0.83]）和TTF（0.64 [0.47；0.86]）独立相关。
在日常实践中FTD/TPI治疗期间生活质量的维持支持其应用。“反应不佳者”的生活质量恶化可能是由于疾病进展。较差的基线生活质量与较短生存期之间的强关联表明，临床医生在确定个体患者的预后和治疗策略时应考虑生活质量。
