Quality-Adjusted Time Without Symptoms of Disease or Toxicity (Q-TWiST) in Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Comparison of Ponatinib Versus Imatinib

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-03-31 DOI:10.1002/cam4.70780

Ajibade Ashaye, Ling Shi, Ibrahim Aldoss, Pau Montesinos, Pankit Vachhani, Vanderson Rocha, Cristina Papayannidis, Jessica T. Leonard, Maria R. Baer, Jose-Maria Ribera, James McCloskey, Jianxiang Wang, Deepali Rane, Shien Guo

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引用次数: 0

Abstract

Background

In the phase 3 ponatinib-3001 trial (PhALLCON, NCT03589326), ponatinib demonstrated superior efficacy over imatinib with comparable safety in patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). This post hoc analysis evaluated the net benefits of ponatinib using a quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) approach.

Methods

Overall survival (OS) time for patients from PhALLCON was partitioned into three health states: TOX (time with grade 3+ treatment-emergent adverse events [TEAEs] before disease progression), TWiST (time without toxicity before progression), and REL (time from progression until death or end of follow-up). Q-TWiST was calculated as the sum of health utility-weighted restricted mean durations of the three states. A relative Q-TWiST gain of ≥ 10% was considered clinically important. Sensitivity analyses were conducted by varying TOX and REL utilities, follow-up time, and the TOX definition (using grade 2+ TEAEs or patient-perceived treatment tolerability assessed by the FACT-GP5).

Results

Among all randomized patients (ponatinib n = 164, imatinib n = 81), restricted mean OS was similar between arms (1082.2 vs. 1024.8 days; p = 0.373). In the base-case analysis, mean TWiST was 214.5 days longer with ponatinib versus imatinib (95% CI 70.3–358.7; p = 0.004), REL was shorter by 175.9 days (325.4–26.5; p = 0.021), and TOX was not significantly different between arms (p = 0.228). The relative Q-TWiST gain (10.98%) was clinically important. Sensitivity analyses consistently supported the robustness of the base-case findings.

Conclusion

Ponatinib may prolong quality-adjusted survival compared with imatinib, supporting the benefit–risk profile of ponatinib as a front-line treatment for Ph+ ALL.

Trial Registration

NCT03589326

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新诊断费城染色体阳性急性淋巴细胞白血病患者无疾病症状或毒性（Q-TWiST）的质量调整时间：波纳替尼与伊马替尼的比较

在3期ponatinib-3001试验（PhALLCON, NCT03589326）中，ponatinib在新诊断的费城阳性急性淋巴细胞白血病（Ph+ ALL）患者中显示出优于伊马替尼的疗效和相当的安全性。本事后分析采用无疾病症状或毒性的质量调整时间（Q-TWiST）方法评估了波纳替尼的净收益。方法将PhALLCON患者的总生存期（OS）分为三种健康状态：TOX（疾病进展前出现3级以上治疗不良事件的时间）、TWiST（进展前无毒性的时间）和REL（从进展到死亡或随访结束的时间）。Q-TWiST计算为三种状态的健康效用加权限制平均持续时间之和。相对Q-TWiST增益≥10%被认为具有重要临床意义。通过不同TOX和REL效用、随访时间和TOX定义（使用2+级teae或FACT-GP5评估的患者感知治疗耐受性）进行敏感性分析。结果在所有随机患者中（波纳替尼n = 164，伊马替尼n = 81），两组间受限平均OS相似(1082.2 vs 1024.8天；p = 0.373)。在基本病例分析中，波纳替尼组的平均TWiST比伊马替尼组长214.5天(95% CI 70.3-358.7；p = 0.004)， REL短175.9天(325.4 ~ 26.5；p = 0.021)，两组间TOX差异无统计学意义（p = 0.228）。相对Q-TWiST增益（10.98%）具有重要的临床意义。敏感性分析一致支持基本病例结果的稳健性。结论与伊马替尼相比，波纳替尼可延长质量调整生存期，支持波纳替尼作为Ph+ ALL一线治疗的获益-风险分析。试验注册编号NCT03589326

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.