Guzauskas Gregory F, Villa Kathleen F, Vanhove Geertrui F, Fisher Vicki L, Veenstra David L
1 Pharmaceutical Outcomes Research and Policy Program, Department of Pharmacy, University of Washington , Seattle, Washington.
2 Jazz Pharmaceuticals , Palo Alto, California.
J Adolesc Young Adult Oncol. 2017 Mar;6(1):53-61. doi: 10.1089/jayao.2016.0049. Epub 2016 Oct 25.
To estimate the risk-benefit trade-off of a pediatric-inspired regimen versus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) for first-line treatment of adolescents/young adult (AYA; ages 16-39 years) patients with Philadelphia-negative acute lymphoblastic leukemia.
Patient outcomes were simulated using a 6-state Markov model, including complete response (CR), no CR, first relapse, second CR, second relapse, and death. A Weibull distribution was fit to the progression-free survival curve of hyper-CVAD-treated AYA patients from a single-center study, and comparable patient data from a retrospective study of pediatric regimen-treated AYA patients were utilized to estimate a relative progression difference (hazard ratio = 0.51) and model survival differences. Health-state utilities were estimated based on treatment stage, with an assumption that the pediatric protocol had 0.10 disutility compared with hyper-CVAD before the maintenance phase of treatment. Total life-years and quality-adjusted life-years (QALYs) were compared between treatment protocols at 1, 5, and 10 years, with additional probabilistic sensitivity analyses.
Treatment with the pediatric-inspired protocol was associated with a 0.04 increase in life-years, but a 0.01 decrease in QALYs at 1 year. By years 5 and 10, the pediatric-inspired protocol resulted in 0.18 and 0.24 increase in life-years and 0.25 and 0.32 increase in QALYs, respectively, relative to hyper-CVAD. The lower quality of life associated with the induction and intensification phases of pediatric treatment was offset by more favorable progression-free survival and overall survival relative to hyper-CVAD.
Our exploratory analysis suggests that, compared with hyper-CVAD, pediatric-inspired protocols may increase life-years throughout treatment stages and QALYs in the long term.
评估以儿科方案为灵感的治疗方案与超分割环磷酰胺、长春新碱、阿霉素和地塞米松（hyper-CVAD）用于一线治疗费城染色体阴性的青少年/青年（AYA；16 - 39岁）急性淋巴细胞白血病患者的风险效益权衡。
使用六状态马尔可夫模型模拟患者预后，包括完全缓解（CR）、未缓解、首次复发、第二次CR、第二次复发和死亡。将威布尔分布拟合到单中心研究中接受hyper-CVAD治疗的AYA患者的无进展生存曲线，并利用儿科方案治疗的AYA患者回顾性研究中的可比患者数据来估计相对进展差异（风险比 = 0.51）并模拟生存差异。基于治疗阶段估计健康状态效用，假设在治疗维持阶段之前，与hyper-CVAD相比，儿科方案有0.10的负效用。在1年、5年和10年时比较治疗方案之间的总生命年和质量调整生命年（QALY），并进行额外的概率敏感性分析。
以儿科方案为灵感的治疗方案在1年时与生命年增加0.04相关，但QALY减少0.01。到第5年和第10年，相对于hyper-CVAD，以儿科方案为灵感的治疗方案分别使生命年增加0.18和0.24，QALY增加0.25和0.32。儿科治疗诱导和强化阶段相关的较低生活质量被相对于hyper-CVAD更有利的无进展生存和总生存所抵消。
我们的探索性分析表明，与hyper-CVAD相比，以儿科方案为灵感的治疗方案可能在整个治疗阶段增加生命年，并在长期内提高QALY。
