Bertaut Aurelie, Touchefeu Yann, Blanc Julie, Bouché Olivier, François Eric, Conroy Thierry, Artru Pascal, Adenis Antoine, Gobbo Jessica, Borg Christophe, Ghiringhelli François, Bennouna Jaafar
Methodology and Biostatistics Unit, Georges-Francois Leclerc Cancer Center, Dijon, France.
Department of Hepatogastroenterology, Digestive Oncology, Nantes Universitary Hospital, Nantes, France.
Clin Colorectal Cancer. 2022 Jun;21(2):e49-e61. doi: 10.1016/j.clcc.2021.09.001. Epub 2021 Oct 3.
We have previously showed that for patients with wild-type RAS metastatic colorectal cancer (mCRC) progressing after bevacizumab plus chemotherapy, bevacizumab continuation plus a switch of chemotherapy is the most appropriate option (PRODIGE 18 phase II study). Here we aimed to determine treatment impact in patient's Health-Related Quality Of Life (HRQoL) in PRODIGE18 study.
HRQoL was evaluated in 2 arms bevacizumab or cetuximab-combined with chemotherapy (modified FOLFOX6 [mFOLFOX6] or FOLFIRI) using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 at baseline, first and third tumor evaluation and at the end of the study. The temporal evolution of quality of life scores was investigated using longitudinal linear mixed models of variance. The time until definitive deterioration (TUDD) was estimated using the Kaplan-Meier method and the long-rank test. A univariate Cox model was used to calculate HR with 95% CI. A multivariate Cox model was applied to determine association of TUDD with age and gender. Safety was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events.
HRQoL QLQ-C30 questionnaire compliance was high at baseline (>90%) and declined over time (∼70% in tumor evaluation 1 and ∼ 60% in tumor evaluation 3), but remained similar in both treatment arms. Patient reported mean diarrhea QLQ-C30 score is significantly higher in bevacizumab treatment arm. Clinician reported mild diarrhea was more frequently declared in bevacizumab treatment arm. Cox multivariate analyses showed no statistically significant differences in TUDD for all QLQ-C30 scales between treatments. TUDD of appetite loss was significantly associated to age.
Our study shows that no relevant impairment of patients HRQoL between the 2 treatment arms. So, the analysis of the HRQoL with equal effectiveness does not make it possible to favor one treatment over another.
我们之前已经表明，对于野生型RAS转移性结直肠癌（mCRC）患者，在贝伐单抗联合化疗后病情进展，继续使用贝伐单抗并更换化疗方案是最合适的选择（PRODIGE 18 II期研究）。在此，我们旨在确定PRODIGE18研究中治疗对患者健康相关生活质量（HRQoL）的影响。
使用欧洲癌症研究与治疗组织（EORTC）QLQ-C30问卷，在基线、首次和第三次肿瘤评估时以及研究结束时，对贝伐单抗或西妥昔单抗联合化疗（改良FOLFOX6 [mFOLFOX6]或FOLFIRI）的两个治疗组进行HRQoL评估。使用纵向线性混合方差模型研究生活质量评分的时间演变。使用Kaplan-Meier方法和长秩检验估计直至明确恶化的时间（TUDD）。使用单变量Cox模型计算95%置信区间的风险比（HR）。应用多变量Cox模型确定TUDD与年龄和性别的关联。通过美国国立癌症研究所不良事件通用术语标准评估安全性。
HRQoL QLQ-C30问卷在基线时的依从性较高（>90%），并随时间下降（肿瘤评估1时约为70%，肿瘤评估3时约为60%），但两个治疗组的情况相似。患者报告的贝伐单抗治疗组平均腹泻QLQ-C30评分显著更高。临床医生报告贝伐单抗治疗组轻度腹泻的发生率更高。Cox多变量分析显示，各治疗组之间所有QLQ-C30量表的TUDD无统计学显著差异。食欲减退的TUDD与年龄显著相关。
我们的研究表明，两个治疗组之间患者的HRQoL没有相关损害。因此，在疗效相同的情况下对HRQoL进行分析并不能使一种治疗优于另一种治疗。
