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 2.9 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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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.