Division of Medical Oncology & Hematology, Bras Drug Development Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada; Autonomous University of Barcelona, Barcelona, Spain.
National Cancer Institute at the National Institutes of Health, Rockville, USA.
Gynecol Oncol. 2022 Nov;167(2):226-233. doi: 10.1016/j.ygyno.2022.08.006. Epub 2022 Aug 30.
A double-blind, randomized, placebo-controlled, phase 2 trial assessed gemcitabine in combination with the wee1 inhibitor adavosertib or placebo in platinum resistant or refractory high grade serous ovarian cancer (HGSOC), demonstrating improved progression free and overall survival favouring the adavosertib/gemcitabine arm. An exploratory objective of the study included the PRO-CTCAE assessment, to capture self-reporting of frequency, severity and/or interference of symptomatic adverse events (syAEs).
PRO-CTCAE items at baseline, days 1 and 15 of each cycle and off treatment, were completed in two centres, with the objective of characterizing syAEs in the first three months of therapy. The maximum post-baseline score proportion for each syAE was tabulated per patient. The 12-week area under the curve (AUC12w) as a measure of syAE over-time and incremental AUC12w (iAUC12w) for adjustment to baseline syAEs.
Sixty-one patients were approached for PRO-CTCAE surveys and 55 were evaluable. Among patients with HGSOC, 28 received gemcitabine/adavosertib (arm A) and 19 gemcitabine/placebo (arm B). Survey completion rates were high. The proportion of participants with positive (≥1) PRO-CTCAE scores was higher for difficulty swallowing with gemcitabine/adavosertib (arm A 35.7% vs arm B 5.3%, p = 0.02). The high score (≥3) syAEs showed more frequent diarrhea with gemcitabine/adavosertib (arm A 25% vs arm B 0%, p = 0.03). The proportions of worsening syAEs over time were higher in patients receiving gemcitabine/adavosertib for difficulty swallowing (arm A 35.7% vs arm B 5.3%; p = 0.03) and fatigue severity (arm A 71.43% vs arm B 42.1%; p = 0.04).
The longitudinal assessment of patient self-reported tolerability showed greater difficulty swallowing and fatigue severity in patients receiving gemcitabine/adavosertib, compared to gemcitabine/placebo. PRO-CTCAE provides complementary and objective assessment of drug tolerability from a patient's perspective.
一项双盲、随机、安慰剂对照、2 期试验评估了吉西他滨联合 wee1 抑制剂adavosertib 或安慰剂在铂耐药或难治性高级别浆液性卵巢癌（HGSOC）中的疗效，结果显示adavosertib/吉西他滨组改善了无进展生存期和总生存期。该研究的一个探索性目标包括 PRO-CTCAE 评估，以捕捉症状性不良事件（syAE）的频率、严重程度和/或干扰的自我报告。
在两个中心完成了基线、每个周期第 15 天和停药时的 PRO-CTCAE 项目，目的是描述治疗前三个月的 syAE。每个患者按每个 syAE 的最大基线后评分比例进行了制表。12 周时的曲线下面积（AUC12w）作为随时间推移的 syAE 测量值，以及调整基线 syAE 的增量 AUC12w（iAUC12w）。
有 61 名患者接受了 PRO-CTCAE 调查，其中 55 名可评估。在 HGSOC 患者中，28 名接受了吉西他滨/adavosertib（A 组）治疗，19 名接受了吉西他滨/安慰剂（B 组）治疗。调查完成率很高。吞咽困难的参与者中，有阳性（≥1）PRO-CTCAE 评分的比例在吉西他滨/adavosertib 组（A 组 35.7%，B 组 5.3%，p=0.02）中更高。高评分（≥3）syAE 显示吉西他滨/adavosertib 组腹泻更频繁（A 组 25%，B 组 0%，p=0.03）。随着时间的推移，吞咽困难和疲劳严重程度恶化的患者比例在接受吉西他滨/adavosertib 治疗的患者中更高，吉西他滨/adavosertib 组（A 组 35.7%，B 组 5.3%；p=0.03）和疲劳严重程度（A 组 71.43%，B 组 42.1%；p=0.04）。
从患者角度对患者自我报告的耐受性进行纵向评估显示，与吉西他滨/安慰剂相比，接受吉西他滨/adavosertib 治疗的患者吞咽困难和疲劳严重程度更大。PRO-CTCAE 从患者角度提供了药物耐受性的补充和客观评估。
