Division of Biostatistics, The Ohio State University College of Public Health, Columbus, OH, USA.
Division of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH, USA.
JNCI Cancer Spectr. 2021 Feb 8;5(2). doi: 10.1093/jncics/pkab018. eCollection 2021 Apr.
Duloxetine effectively treats aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) in women with breast cancer but causes low-grade toxicities. This secondary analysis examines the relationship between adverse events (AE) and patient-perceived benefit, based on patient self-report that the treatment received was beneficial despite side effects. We hypothesized that duloxetine had a favorable effect on patient-perceived benefit, even among duloxetine-treated patients who experienced AEs and who, had they been treated with placebo, would have experienced none.
Principal stratification was used to estimate the effect of duloxetine vs placebo on patient-perceived benefit and Functional Assessment of Cancer Therapy-Endocrine Scale functional quality of life in the randomized, double-blind trial SWOG S1202 (n = 289). Subgroups of patients were defined by observed and counterfactual (what would have occurred had they been randomly assigned to the opposite study arm) experiences of AEs and the original primary outcome, reduction of average pain after 12 weeks of at least 2 points on the Brief Pain Inventory-Short Form.
Duloxetine caused an estimated 23.4% (95% credible interval [CI] = 13.4% to 33.7%) of patients to experience an AE even though they would have experienced none on placebo. Those patients remained more likely to report that their received treatment was beneficial than comparable patients assigned placebo (73.3% vs 41.8%, respectively; 95% CI for difference = 15.4 to 47.2 percentage points), although there was no statistically significant effect of duloxetine on functional quality of life (11.3 vs 9.0, 95% CI for difference = -2.2 to +6.7).
Duloxetine resulted in higher patient-perceived benefit, even among those who would have an AE on duloxetine but none on placebo. Treatment of AIMSS with duloxetine should be considered for appropriate patients.
度洛西汀能有效治疗乳腺癌患者芳香化酶抑制剂相关的肌肉骨骼症状（AIMSS），但其会引起轻微的毒性。这项二次分析基于患者自我报告，即尽管存在副作用，但治疗是有益的，考察了不良事件（AE）与患者感知获益之间的关系。我们假设，即使在接受度洛西汀治疗且发生 AE 的患者中，度洛西汀也会对患者感知获益产生有利影响，如果他们接受安慰剂治疗，则不会发生 AE。
使用主要分层来估计度洛西汀与安慰剂对随机、双盲试验 SWOG S1202（n=289）中患者感知获益和癌症治疗功能评估-内分泌量表功能生活质量的影响。根据观察到的和反事实（如果他们被随机分配到相反的研究臂，会发生什么）AE 经历和原始主要结局（12 周后 Brief Pain Inventory-Short Form 平均疼痛减少至少 2 分），将患者分为亚组。
即使在安慰剂治疗时不会发生 AE，度洛西汀仍导致估计 23.4%（95%可信区间[CI] = 13.4%至 33.7%）的患者发生 AE。与接受安慰剂的可比患者相比，这些患者更有可能报告他们接受的治疗是有益的（分别为 73.3%和 41.8%；差异的 95%CI 为 15.4 至 47.2 个百分点），尽管度洛西汀对功能生活质量没有统计学显著影响（11.3 与 9.0，差异的 95%CI 为 -2.2 至 +6.7）。
即使在接受度洛西汀会发生 AE 而接受安慰剂则不会发生 AE 的患者中，度洛西汀也会导致更高的患者感知获益。对于合适的患者，应考虑使用度洛西汀治疗 AIMSS。
